Category Archives: Stem Cell Treatment

Discovery could revolutionize stem cell-based brain repair therapy for Parkinson’s disease – News-Medical.Net

Neuroscientists at University of Galway have made an exciting discovery that could revolutionize stem cell-based brain repair therapy for Parkinson's disease.

Parkinson's is a neurodegenerative condition in which brain cells slowly degenerate and die leading to a progressive deterioration in a person's ability to control movement. It is estimated that there are 8.5 million people living with the condition worldwide, and 12,000 people in Ireland alone.

Brain repair for Parkinson's involves replacing the dead cells by transplanting healthy brain cells back into the brain. With recent advancements in regenerative medicine and stem cell technology, "induced stem cells" can now be used as a source of healthy cells.

Induced stem cells are reprogrammed from adult cells, such as skin cells, and can be converted in the laboratory into the appropriate type of brain cell required for repairing the Parkinson's brain.

However, these skin cells-turned brain cells need to be transplanted into the brain at a very early stage in their conversion, and the vast majority of the cells do not continue to convert -once in the brain - into the mature cells that are required for the therapy to work.

In work funded by The Michael J. Fox Foundation for Parkinson's Research (MJFF) and Science Foundation Ireland, published this week in the Journal of Neural Engineering, the team in the College of Medicine, Nursing and Health Sciences at University of Galway have shown that transplanting the immature cells in a collagen hydrogel dramatically improves both their survival and maturation in the brain.

Commenting on the research finding, the lead neuroscientist on the project, Professor Eils Dowd, said:"Our hydrogel nurtures, supports and protects the cells after they are transplanted into the brain, and this dramatically improves their maturation and reparative ability. Ultimately, we hope that continued development of this promising gel will lead to a significant improvement in brain repair approaches for people living with Parkinson's."

The Michael J. Fox Foundation awarded $300,000 to continue the development of the hydrogel.

The new research aims to understand how the immune system in the brain reacts when cells are transplanted alone versus when they are transplanted in combination with the hydrogel.

The research will continue to be led by Professor Dowd, in collaboration with colleagues from CRAM - the Science Foundation Ireland Research Centre for Medical Devices based at University of Galway, the University of Edinburgh and the University of Melbourne.

Professor Dowd's ongoing research in this field is featured in the short documentary Feats of Modest Valourwhich won the coveted Scientist Award at the Imagine Science Film Festival in New York, as well as the Professional Documentary Award at the Raw Science Festival in California.

Source:

Journal reference:

Comini, G.,et al.(2024) Survival and maturation of human induced pluripotent stem cell-derived dopaminergic progenitors in the Parkinsonian rat brain is enhanced by transplantation in a neurotrophin-enriched hydrogel.Journal of Neural Engineering.doi.org/10.1088/1741-2552/ad33b2.

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Discovery could revolutionize stem cell-based brain repair therapy for Parkinson's disease - News-Medical.Net

Scientists Uncover Cause of Inherited Bone Marrow Failure – Mirage News

An international study led by researchers from Children's Hospital of Philadelphia (CHOP) has discovered an important biological cause of Fanconi anemia, a rare inherited disorder that almost universally leads to bone marrow failure. The researchers also confirmed that a readily available bile acid may help correct some of these biological issues and provide more options for potential treatment. The findings were recently published by the journal Nature Communications.

Fanconi anemia was discovered nearly a century ago. Over the course of decades of study, researchers had previously linked Fanconi anemia to DNA damage that impairs the function of hematopoietic stem cells (HSCs), which are responsible for lifelong function and renewal of blood cells. DNA damage leads to cell death and eventually gives way to frank bone marrow failure. Since stem cells are impacted, a stem cell transplant is the only treatment currently available for Fanconi anemia. However, not all patients have matching donors, and those who do can still experience side effects from the treatment.

Prior research by the group revealed that the loss of stem cells that leads to Fanconi anemia begin before birth, making the underlying biology behind this condition very difficult to study. Using mouse models and a combination of other techniques, researchers were able to determine the events before birth that eventually accelerate bone marrow failure by early school age in these patients.

Peter Kurre, MD "Fanconi anemia is thought to be a DNA disorder, and those who have been researching it have focused solely on this aspect," said senior author Peter Kurre, MD, Director of the Pediatric Comprehensive Bone Marrow Failure Center at CHOP. "What our research demonstrates for the first time is that Fanconi anemia is caused by an accumulation of misfolded proteins that preclude proper cell cycle progression and stem cell expansion, which in turn leads to rapid bone marrow failure after birth."

The study found that increased protein synthesis rates in fetal HSCs occur at the onset of Fanconi anemia. The proteins are misfolded in fetal liver HSCs, which leads to stress on the endoplasmic reticulum, a network of tubules in our cells responsible for producing healthy proteins needed for a variety of functions. This accumulation of misfolded proteins confers cellular stress signals that slow down cell cycle progression and emergence of a sufficient number of stem cells, causing rapid bone marrow failure early in life.

With this new knowledge of the mechanisms behind Fanconi anemia, the researchers then used tauroursodeoxycholic acid (TUDCA), a bile salt that has been studied for use in preventing and treating gallstones and helping to reduce the side effects associated with certain inflammatory disorders. In HSC of the Fanconi anemia animal model, TUDCA restored proper protein folding.

"When TDUCA was given, we were able to confirm the restoration of folding as well as improved function of the stem cells," said Narasaiah Kovuru, PhD, a postdoctoral researcher in the Kurre Laboratory and first author of the study.

With this combination of information, the researchers determined that the degradation of protein homeostasis - the proper regulation of proteins in these cells - is driven by excess inflammatory activity in HSCS within the fetal liver, and dampening this activity helps restore HSCs to their normal numbers.

"Regulating protein production, folding and degradation properly is like the story of Goldilocks and the Three Bears, in that too much or too little protein is a problem, and the levels need to be just right for proper function," Kurre said. "This study reveals the direction our research should go next to determine what mechanisms are at play that alter these protein levels and what alternate treatment options we might be able to develop for patients for whom stem cell transplantation is not an option."

This study was supported by National Institutes of Health grant R01-HL150882.

Kovuru et al, "Deregulated protein homeostasis constrains fetal hematopoietic stem cell pool expansion in Fanconi anemia." Nat Commun. Online February 29, 2024. DOI: 0.1038/s41467-024-46159-1.

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Scientists Uncover Cause of Inherited Bone Marrow Failure - Mirage News

Collagen hydrogel can boost survival of precursor neurons to brain – Parkinson’s News Today

Encapsulating precursor nerve cells in a collagen hydrogel can enhance the efficacy of stem cell transplantation to the brain, a potential treatment to replace dopamine-producing nerve cells that are lost in people with Parkinsons disease, according to a preclinical study.

Our hydrogel nurtures, supports and protects the cells after they are transplanted into the brain, and this dramatically improves their maturation and reparative ability, Eils Dowd, PhD, study lead at the College of Medicine, Nursing and Health Sciences at the University of Galway, in Ireland, said in a university press release.

Ultimately, we hope that continued development of this promising gel will lead to a significant improvement in brain repair approaches for people living with Parkinsons, Dowd said.

The study, Survival and maturation of human induced pluripotent stem cell-derived dopaminergic progenitors in the Parkinsonian rat brain is enhanced by transplantation in a neurotrophin-enriched hydrogel, supported by research grants from The Michael J. Fox Foundation for Parkinsons Research (MJFF), was published in the Journal of Neural Engineering.

Parkinsons symptoms are caused by the progressive loss of dopaminergic neurons, the specialized nerve cells that produce dopamine, a chemical messenger in the brain.

Cell-based brain repair is a promising therapeutic approach for Parkinsons disease, whereby the lost dopaminergic neurons are replaced by the transplantation of healthy neurons. Such neurons can be derived from induced pluripotent stem cells, or iPSCs, that are reprogrammed from adult cells, such as skin cells, and converted into dopaminergic neurons.

In fact, stem cell-based therapies have already started clinical testing, including a trial evaluating bemdaneprocel, which demonstrated sustained efficacy 1.5 years after treatment, and another called STEM-PD.

However, iPSCs need to be transplanted into the brain very early in their maturation from stem cells to fully functional neurons. Even so, most transplanted cells do not fully mature into dopaminergic neurons once they are inside the brain.

Thus, it is imperative to continue rigorous preclinical studies to identify methods to improve their outcome to maximise their reparative/reconstructive potential, Dowd and her colleagues wrote.

Encapsulating cells in hydrogels made with collagen, the most abundant protein in connective tissue, has the potential to address many limitations of transplantation. These hydrogels act as a scaffold, shielding cells from immune responses, and can be infused with neurotrophic factors, proteins that induce the survival, development, and function of neurons.

Ultimately, we hope that continued development of this promising gel will lead to a significant improvement in brain repair approaches for people living with Parkinsons.

In previous work, Dowds team encapsulated primary dopaminergic neurons in a collagen hydrogel loaded with a neurotrophic factor called GDNF. Transplantation with the specialized gel dramatically increased the survival and function of these cells in a rat model of Parkinsons.

In this new study, the researchers tested the gel method using dopaminergic precursor cells (DAPs) derived from iPSCs (iPSC-DAPs). Cells were transplanted into the brain of a Parkinsons rat model, with or without the gel, and with or without the neurotrophic factors GDNF and BDNF.

Surviving iPSC-derived cells were visible in all four groups as early as one week after transplantation. Still, the graft cells were significantly larger in the two groups treated with iPSC-DAPs in the hydrogel, with or without neurotrophic factors, than in the two groups without the hydrogel.

This suggested not only was the hydrogel cytocompatible with these cells, the beneficial effects of the gel were already manifesting shortly after transplantation, the researchers wrote.

Although the cells transplanted with the hydrogel stimulated a broader immune response, the researchers noted this was likely a reflection of the larger graft size in the hydrogel groups.

As assessed 20 weeks, or 4.6 months, after transplantation, neurotrophic-enriched iPSC-DAPs in the hydrogel were larger and more dispersed within the brain compared with cells transplanted alone, which were small and compact. When transplanted with the neurotrophic-enriched hydrogel, cell survival increased eightfold, and dopaminergic neuron maturation improved 16 times higher.

Comparably, significantly more iPSC-DAPs matured into dopaminergic neurons with the enriched hydrogel than without (11.2% vs. 2.1%). Furthermore, one in six rats given cells alone reached a dopaminergic maturation level of more than 5%, whereas all seven rats treated with enriched cells in the hydrogel achieved this outcome.

This suggests that the neurotrophin-enriched hydrogel is having a beneficial effect on dopaminergic differentiation and maturation over and above the effect on progenitor survival, the team wrote.

Given the beneficial effects of this hydrogel on human iPSC-derived brain repair in this Parkinsonian rat model, further development of such hydrogel carriers is warranted to improve the survival, differentiation and overall outcome of stem cell-derived brain repair in Parkinsons patients, the researchers concluded.

Further development of the hydrogel, specifically to understand how the immune system in the brain reacts upon transplantation, is being supported by a $300,000 award from the MJFF.

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Collagen hydrogel can boost survival of precursor neurons to brain - Parkinson's News Today

Notoginsenoside R1 promotes Lgr5+ stem cell and epithelium renovation in colitis mice via activating Wnt/-Catenin … – Nature.com

Chemicals and reagents

Notoginsenoside R1 (NGR1, BP1010, C47H80O18, purity 98%, CAS No 80418-24-2, MW: 933.13Da) was purchased from Chengdu Purifa Technology Development Co. Ltd (Chengdu, China). Dextran sulfate sodium salt (DSS, 0216011010, MW: 36kDa50kDa) was purchased from MP Biomedicals (Shanghai, China). Salicylazosulfapyridine (SASP, S0883, C18H14N4O5S, CAS No 599-79-1, MW: 398.39Da) and FITC-dextran (FD4, CAS No 60842-46-8) was purchased from Sigma-Aldrich (Darmstadt, Germany). ICG-001 (T6113, C33H32N4O4, purity 98%, CAS No 780757-88-2, MW: 548.64Da) was acquired from TOPSCIENCE (Shanghai, China). Water-DEPC treated (693520) and DMSO (D8418) were obtained from MilliporeSigma (Burlington, MA, USA).

NCM460 human intestinal epithelial cells and CT26 murine colon carcinoma cells were obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA). NCM460 and CT26 cells were cultured in Roswell Park Memorial Institute (RPMI)-1640 culture medium (11875085, Gibco, NY, USA) supplemented with 10% fetal bovine serum (10099158, Gibco, NY, USA). The culture conditions included a humidified atmosphere containing 5% CO2, with a constant temperature maintained at 37C.

The Laboratory Animal Center of Shanghai University of Traditional Chinese Medicine provided female C57BL/6 mice weighing 202g. These mice were housed in a specific pathogen-free facility under meticulously controlled conditions, including a temperature range of 2325C, humidity maintained at 60%70%, and a well-regulated 12-h light-dark cycle. The Animal Experimentation Ethics Committee of Shanghai University of Traditional Chinese Medicine granted approval (PZSHUTCM2307310004) for experimental procedures conducted on the animals. All experiments were conducted in accordance with institutional animal care guidelines and protocols approved by the committee.

According to the method reported by Yue [26], we established the acute colitis mouse model. Briefly, female C57BL/6 mice were divided randomly into four groups: Control, DSS, DSS+SASP, and DSS+NGR1. Acute colitis was induced by administering 3% DSS in the drinking water of mice for a period of 8 days. Mice in the DSS+SASP group were treated orally with SASP (260mg/kg) once per day for the same duration. The DSS+NGR1 group received NGR1 (25, 50, 125mg/kg) by oral gavage once per day for 10 days. Mice in the Control and DSS groups were administered the same volume of Control. Daily monitoring of body weight and rectal bleeding was conducted throughout the 10-day period. At the end of the experiment, mice were euthanized, and the colon was collected for further analysis.

Female C57BL/6 mice were randomly divided into four groups: DSS, DSS+ICG-001, DSS+NGR1 and DSS+ICG-001+NGR1. To establish an acute enteritis model, mice were subjected to the protocol described above. Mice in the DSS+NGR1 and DSS+ICG-001+NGR1 group were given NGR1 (25mg/kg) orally once daily for 10 consecutive days. Meanwhile, mice in the DSS+ICG-001 and DSS+ICG-001+NGR1 groups were given ICG-001 (20mg/kg) via intraperitoneal injection three times per week. The DSS and DSS+NGR1 groups received the same volume of Control.

Male BALB/c mice were acclimated for 1 week in a specific pathogen-free environment. Subsequently, CT26 cells (2105 cells/mouse) were subcutaneously transplanted into the left axillary region of each mouse. Once the tumor size reached 200mm3, the mice were randomly assigned to the vehicle group or the NGR1 group based on tumor size. Throughout the 18-day experiment, mice in the vehicle group received 0.5% CMC-Na, while those in the NGR1 group were administered 25mg/kg NGR1. Tumor volume=0.5length (mm)width (mm)2.

C57BL/6 mice were fasted for 4h before execution. Mice were then orally administered 60mg/100g body weight of FITC-dextran in 200L of sterile saline. After 4h, blood samples were collected via retro-orbital bleeding, and serum was separated by centrifugation. The serum FITC-dextran levels were measured at an excitation wavelength of 485nm and an emission wavelength of 528nm using a fluorometer (VARIOSKAN FLASH, Thermo Fisher, MA, USA).

Colonic tissues were collected from mice and fixed in 4% paraformaldehyde. Tissues were then dehydrated, embedded in paraffin, and sectioned into 4m thick slices. The sections were then stained with hematoxylin and eosin (H&E) using standard protocols. Stained sections were analyzed under a light microscope (BX61VS, Olympus, Tokyo, Japan), and images were captured for further analysis.

The concentrations of DAO (CSB-E10090m) and LPS (CSB-E13066m) in mouse serum samples were determined using the respective ELISA kit (Wuhan Huamei Biological Engineering Co., Ltd, Wuhan, China). Specifically, serum samples were added to a 96-well plate coated with DAO or LPS-specific antibodies, followed by incubation with detection reagents and substrate solution. Absorbance was measured at 450nm, and concentrations were calculated using standard curves.

Colonic tissues were fixed in 4% paraformaldehyde, embedded in OCT compound, and sectioned into 5-m slices. After permeabilization and blocking, sections were incubated with primary antibodies against ZO-1 (#13663, Cell Signaling Technology, CST, MA, USA) and Occludin (#91131, CST, MA, USA), followed by secondary antibodies conjugated to fluorophores (9300039001, ABclonal, Wuhan, China). Nuclei were counterstained with DAPI (#4083, CST, MA, USA), and images were obtained using a fluorescence microscope (BX61VS, Olympus, Tokyo, Japan). Quantification of ZO-1 and Occludin expression was performed using ImageJ software (NIH, Bethesda, MD, USA).

Colonic tissue samples were obtained from mice, fixed, dehydrated, embedded in paraffin blocks, sectioned, and stained with Alcian blue using a commercial kit. Under a light microscope (BX61VS, Olympus, Tokyo, Japan), the stained sections were examined and images were captured for subsequent analysis.

RNA was extracted using the TRIzol method, and RNA quantity and purity were measured by NanoDrop spectrophotometer (Thermo Fisher Scientific). The RNA was then reverse-transcribed using an Evo M-MLV RT Premix for qPCR kit (AG11706, Accurate Biotechnology Co., Ltd., Chengdu, China), and qPCR was performed using a SYBR Green Premix Pro Taq HS qPCR Kit (AG11718, Accurate Biotechnology Co., Ltd., Chengdu, China) (Table1). The amplification was carried out using an ABI Prism 7900HT Sequence Detection System (Life Technologies, CA, USA), and data were analyzed using the 2Ct method.

Colonic tissues were extracted and homogenized, and protein was obtained using RIPA lysis buffer with phosphatase and protease inhibitors. Protein concentration was measured using a BCA assay kit (20201ES76, Yeasen Biotech Co., Ltd, Shanghai, China). Equal amounts of protein were loaded onto SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) gels and separated by electrophoresis. Subsequently, the separated proteins were transferred onto PVDF membranes (000025736, Milipore, MA, USA). The membrane was then blocked with 5% BSA solution for 2h. After blocking, the membrane was incubated with primary antibodies overnight at 4C, followed by incubation with HRP-conjugated secondary antibodies for 1h at room temperature. Protein bands were visualized using ECL reagents (WBKLS0500, Millipore) and imaged with a GS-700 imaging densitometer (Bio-Rad, CA, USA). Protein expression levels were quantified using ImageJ software (NIH, Bethesda, MD, USA). The following primary antibodies were used: rabbit anti--Catenin (1:1000, #8480, CST, MA, USA), rabbit anti-p-GSK-3 (1:1000, #5558, CST, MA, USA), rabbit anti-GSK-3 (1:1000, #12456, CST, MA, USA), rabbit anti-Cyclin D1 (1:1000, #2922, CST, MA, USA), rabbit anti-c-Myc (1:1000, #5605, CST, MA, USA) and rabbit anti--actin (1:1000, #4970, CST, MA, USA).

Colonic tissue sections were fixed in 4% paraformaldehyde, embedded in paraffin, and sliced into 5m thick sections. Antigen retrieval was performed using citrate buffer solution (pH=6.0) and heating in a microwave oven. Non-specific binding was blocked with 5% goat serum for 30min. Sections were incubated overnight at 4C with primary antibodies, followed by incubation with a secondary antibody and staining with DAB (3,3-diaminobenzidine). Hematoxylin was used for counterstaining before the sections were examined microscopically and images were captured.

Total RNA was extracted from mouse intestinal tissues using TRIzol reagent according to the manufacturers instructions. The extracted RNA was evaluated for quality using a NanoDrop spectrophotometer (Thermo Fisher). RNA sequencing libraries were then constructed with the NEBNext Ultra RNA Library Prep Kit for Illumina, and sequencing was performed on an Illumina HiSeq platform. The differential gene was carried out on the cloud platform of majorbio (https://www.majorbio.com/).

Caco-2 cells were seeded in Millicell inserts of 24-well plates at a density of 5104 cells/400L per well. The outer chamber was filled with 600L DMEM medium (2323012, Gibco, NY, USA) and replaced every other day. TEER values were measured using a MERS00002 volt-ohm meter system (Milipore), and the electrode was sterilized with 70% ethanol and rinsed with sterile phosphate-buffered saline (PBS) before each measurement. Monolayer formation was assumed at TEER values of 400/cm2. Measurements were taken at regular intervals using the same electrode and recorded.

The intestinal crypts were isolated from the small intestine of C57BL/6 mice (6- to 8-week-old). The small intestine was removed and flushed with ice-cold PBS. The intestine was opened longitudinally and cut into 2- to 3-mm pieces. The pieces were then washed with ice-cold PBS and incubated in 3mM EDTA solution at 4C for 20min with gentle shaking. After incubation, the crypts were released by vigorously shaking the tubes. The supernatant containing the crypts was collected and filtered through a 70-m cell strainer. The crypts were then centrifuged at 1200r/min for 5min and resuspended in Matrigel (Corning, NA, USA). The crypt-Matrigel mixture was plated in 24-well plates and incubated at 37C for 30min to allow the Matrigel to solidify. The IntestCultTM OGM Mouse Basal Medium (#06005, STEMCELL, Vancouver, Canada) was then added to the wells and changed every other day.

After cultured 2 days in a 24 well plate, the intestinal crypts were randomly divided into control, DSS model group and DSS+NGR1 group. Then, the organoids were administered DSS (20g/mL), DSS (20g/mL) plus NGR1 (100M) for 4 days. The organoid growth conditions were recorded by the microscope (Olympus CKX4, Tokyo, Japan). IHC assay was conducted to examine the fluorescent protein expression of Lgr5 and -Catenin (refer to the above method of IHC).

The molecular docking was performed using AutoDock Vina software. The 3D crystal structure of -Catenin protein (PDB: 1JDH) was obtained from the Protein Data Bank (PDB) database. The structure of NGR1 was drawn and optimized using ChemDraw software and converted to a PDB file using Open Babel software. The protein and ligand files were prepared using AutoDock Tools. Docking simulations were performed and the conformation with the lowest binding energy was selected as the final docking result. The docking results were analyzed using PyMOL software.

The TOPFlash assay was performed as previously described with slight modifications [27]. HEK293T cells were seeded in 24-well plates and cultured overnight. The cells were transfected with the 500ng TOPFlash luciferase reporter plasmids (Beyotime Biotechnology, Shanghai, China) and 50ng Renilla luciferase (Promega GmbH, Mannheim, Germany) using Lipofectamine 3000 (Thermo Fisher). After 24h, the cells were treated with NGR1 (50M) and BIO (0.5M) for 24h, separately. Subsequently, cells were lysed in 150L/well passive phenylbenzothiazole (PPBT) buffer, and the luciferase activity was measured using a Dual-LuciferaseTM Reporter Assay System (Promega Corporation, WI, USA). The firefly luciferase activity was normalized to Renilla luciferase activity.

A scratch wound was created using a plastic pipette (10L) tip. NCM460 cells were then washed with PBS to remove any debris and treated with either DSS (20g/mL) or DSS (20g/mL)+NGR1 (100M) for 24h. The width of the scratch was measured using microscopy at 0 and 24h post-dosing, and the percentage of wound closure was calculated by comparing the scratch width at 24h to the initial scratch width.

NCM460 cells were treated with either DSS (20g/mL) or DSS (20g/mL)+NGR1 (100M) for 24h. Then, NCM460 cells were harvested and washed with PBS after experimental treatment. Cells were then suspended in a binding buffer containing Annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI), and incubated in the dark at room temperature for 15min. Flow cytometry analysis was performed to detect apoptotic cells. The data were analyzed using Guava software, and the percentage of apoptotic cells was expressed.

Statistical analysis was performed using GraphPad Prism 9.0 software. Data were presented as meanstandard deviation (SD). Differences between groups were analyzed using one-way analysis of variance (ANOVA). P<0.05 was considered statistically significant. All experiments were repeated at least three times.

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Notoginsenoside R1 promotes Lgr5+ stem cell and epithelium renovation in colitis mice via activating Wnt/-Catenin ... - Nature.com

BioCardia and StemCardia Announce Biotherapeutic Delivery Partnership – Diagnostic and Interventional Cardiology

March 15, 2024 BioCardia, Inc., a biotechnology company focused on advancing late-stage cell therapy interventions for cardiovascular disorders, andStemCardia, Inc., a biotechnology company focused on cell and gene therapy to re-muscularize the failing heart, today announced a long-term partnership to advance StemCardias investigational pluripotent stem cell product candidate for the treatment of heart failure.

Under the partnership, BioCardia is the exclusive biotherapeutic delivery partner for StemCardias cell therapy candidate through studies expected to result in FDA approval of an investigational new drug application (IND) and the anticipated Phase I/II clinical development to follow.

BioCardia has established safe and minimally invasive delivery of cellular medicines directly into the heart, said Chuck Murry, MD, PhD, StemCardias Founder and CEO. Having worked with BioCardia to successfully deliver our bona fide cardiac muscle cells in large animal models of heart failure, we are excited for this partnership to accelerate clinical development and broaden future commercial access to an off-the-shelf heart regeneration treatment.

StemCardias team encompasses recognized leaders in the field of cardiac regenerative medicine who are pursuing an elegant strategy to repair the failing heart. We look forward to supporting their efforts with our experienced team and proven, proprietary Helixbiotherapeutic delivery system, said BioCardia CEO Peter Altman, PhD. This partnership is expected to enhance future treatment options for millions of people suffering from heart failure, offset the costs of biotherapeutic delivery development for our own programs, and provide our investors with meaningful revenue sharing should our efforts together contribute to StemCardias successful therapeutic development.

For more information:www.biocardia.com

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BioCardia and StemCardia Announce Biotherapeutic Delivery Partnership - Diagnostic and Interventional Cardiology

Lawsuit over League City stem-cell treatment headed for trial – Galveston County Daily News

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Lawsuit over League City stem-cell treatment headed for trial - Galveston County Daily News

Developing Stem Cell Therapy to Halt Critical Limb Amputations – Mirage News

Critical limb ischemia is a condition in which the main blood vessels supplying blood to the legs are blocked, causing blood flow to gradually decrease as atherosclerosis progresses in the peripheral arteries. It is a severe form of peripheral artery disease that causes progressive closure of arteries in the lower extremity, leading to the necrosis of the leg tissue and eventual amputation. Current treatments include angioplasty procedures such as stent implantation and anti-thrombotic drugs, but there is a risk of blood vessel damage and recurrence of blood clots, which is why there is a strong interest in developing a treatment using stem cells.

A research team led by Dr. Sangheon Kim of the Center for Biomaterials Research at the Korea Institute of Science and Technology (KIST) announced that they have developed a three-dimensional stem cell therapy to treat critical limb ischemia through a self-assembling platform technology using a new material microgel. By using collagen microgels, a new biocompatible material, the researchers were able to easily transplant stem cells into the body and increase cell survival rate compared to 3D stem cell therapies made of cells alone.

Stem cell therapies have high tissue regeneration capabilities, but when stem cells are transplanted alone, hypoxia at the site of injury, immune responses, and other factors can reduce cell viability and prevent the desired therapeutic effect. Therefore, it is necessary to develop a material that delivers stem cells using biodegradable polymers or components of extracellular matrix as a support to increase cell viability.

The team processed collagen hydrogels to micro-scale to create porous, three-dimensional scaffolds that are easy to inject in the body and have a uniform cell distribution. Collagen, a component of the extracellular matrix, has excellent biocompatibility and cellular activity, which can induce cell self-assembly by promoting interactions between the microgel particles and collagen receptors on stem cells. In addition, the spacing between microgel particles increased the porosity of the three-dimensional constructs, improving delivery efficiency and cell survival.

The microgel-cell constructs developed by the researchers expressed more pro-angiogenic factors and exhibited higher angiogenic potential than cell-only constructs. When microgel-cell constructs were injected into the muscle tissue of mice with critical limb ischemia, blood perfusion rate increased by about 40% and limb salvage ratio increased by 60% compared to the cell-only constructs, confirming their effectiveness in increasing blood flow and preventing necrosis in the ischemic limb.

The new stem cell therapy is expected to provide a new alternative for patients with critical limb ischemia who have limited treatment options other than amputation due to its excellent angiogenic effect. Furthermore, since angiogenesis is an essential component of various tissue regeneration processes, it can be extended to other diseases with similar mechanisms to peripheral arterial disease.

"The collagen microgel developed in this study is a new biomaterial with excellent biocompatibility and high potential for clinical applications," said Dr. Sangheon Kim of KIST. "We plan to develop technologies for administration methods required in the medical field, as well as conduct follow-up research to clarify the clear mechanism of action of the treatment and discover target factors."

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Developing Stem Cell Therapy to Halt Critical Limb Amputations - Mirage News

Cell therapy for retinal degenerative disorders: a systematic review and three-level meta-analysis – Journal of … – Journal of Translational…

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Trends in Stem Cell Transplantation Refusal for Myeloma Treatment – Targeted Oncology

Determining the right path for multiple myeloma treatment is often complex as various decisions can significantly impact patient outcomes. Among these decisions, the consideration of autologous hematopoietic stem cell transplantation (HSCT) stands as a cornerstone, offering hope for improved progression-free and overall survival. However, recent research from Chakra Chaulagain, MD, showed that a small yet significant percentage of patients are refusing this potentially life-saving procedure.

An analysis of National Cancer Database (NCDB) data presented at the 2023 American Society of Hematology Annual Meeting showed that of 43,653 patients with newly diagnosed multiple myeloma recommended for HSCT, 98.05% proceeded with the procedure. However, the remaining 2% opted out. Some of the key factors influencing the patient's decision regarding HSCT related to socioeconomic, racial, and geographic disparities.

According to Chaulagain, director of the multiple myeloma and amyloidosis program at Cleveland Clinic Florida, older patients with multiple myeloma, those with comorbidities, and those lacking robust insurance coverage are more likely to decline HSCT. Furthermore, Black patients exhibited higher rates of refusal compared with White patients (OR, 1.38; P =.0022).

These findings underscore the need for future studies and policy changes to address socioeconomic and racial disparities in access to transplantation.

In an interview with Targeted OncologyTM, Chaulagain discussed the trends of rates of autologous HSCT refusal among patients with multiple myeloma.

Targeted Oncology: What led to your research on autologous HSCT refusal rates among patients with multiple myeloma?

Chaulagain: There is minimal data on real-world findings about refusal of a standard-of-care, for example, stem cell transplantation in [patients with] multiple myeloma. We wanted to explore some ideas about what are the factors that are contributing to the refusal transplant, which is the current standard-of-care, and it is known to improve both progression-free and overall survival based on randomized clinical trials. But there is limited real-world data around this subject, so we decided to investigate the NCDB.

Tumor microenvironment background with cancer cells, T-Cells, nanoparticles, molecules, and blood vessels. Oncology research concept: ratatosk - stock.adobe.com

What were the methods and design of this analysis?

This is a retrospective analysis of a very large number of [patients with] multiple myeloma that were treated by a commission of cancer-accredited cancer centers throughout the United States. There are at least 1500 of these types of cancer centers, and they report to this NCDB, where they have all of this data collected. NCDB captures about 70% of all cancer cases in the United States. We decided to get those data and analyze them just for multiple myeloma with the purpose of finding what are the variables and clinical factors that are responsible for refusal of autologous stem cell transplantation in [patients with] myeloma.

What were the key findings regarding the utilization of autologous HSCT in patients with multiple myeloma?

We had 43,600 patients [with] newly diagnosed multiple myeloma, and they were recommended to undergo a stem cell transplantation after completing their initial induction therapy by their doctors. Ninety-eight percent of the patients did go and do the stem cell transplantation, but 2% refused. We analyzed the various socioeconomic, racial, ethnic, and geographic factors about what made them refuse the stem cell transplantation.

Did the study identify any patient subgroups who were more likely to refuse?

We did find that older patients had a higher odds of refusing essential transplantation. Male [patients] had higher odds of accepting transplantation and females had higher odds of refusing it. Patients with more major medical comorbidities had higher odds of refusing it. Patients without insurance, or Medicare and Medicaid, had higher odds of refusing stem cell transplantation compared with patients who had private insurance. Median household income was also a significant predictor of whether the patient will go for a stem cell transplant or not. Those who were earning less than $63,000 annually had a higher odds of refusing autologous stem cell transplantation. Black patients, for example, had a higher odds of refusing transplantation, and Hispanic [patients] had a lower odds of refusing transplantation.

Were there any significant trends in the refusal rates over this time period?

The study time point was from 2004 until 2020. Patients who were diagnosed and treated closer to 2020 had a higher odds of refusing transplantation, and patients who were diagnosed closer to 2004 had a higher odds of accepting transplantation or lower odds of refusing transplantation, and we think it may have to do with advancement in novel therapies, particularly monoclonal antibody therapies in multiple myeloma in the current years.

What are the potential reasons as to why patients refused more than others?

The higher age, decreased income, not having strong private insurance, and also, the facility type did matter. For example, patients who were treated at nonacademic facilities had a higher odds of refusing transplant compared with patients that were treated at academic centers. There was also regional variation on whether the patient would refuse or accept transplant. For example, in South Atlantic states in the United States, patients had higher odds of refusing transplantation.

What are the implications of these findings?

We found that there was significant variation across the United States in terms of racial, economic, and geographic variation, and this data can and should be used for designing future clinical studies in a prospective basis.

How have recent advancements in the multiple myeloma space such as the emergence of novel therapies impacted transplantation?

Based on our studies, the emergence of novel therapies and immunotherapy, particularly anti-CD38 monoclonal antibodies like daratumumab [Darzalex], have led to decrease utilization of transplant, and it will probably further evolve down the road because of the availability of even more effective novel therapies such as [chimeric antigen receptor] T-cell therapy, and bispecific T-cell engager therapy. The role of transplant will continue to evolve and will probably continue to diminish down the road.

What barriers still need to be addressed regarding transplant?

These are bigger decisions at the policy and procedure and legislation [levels], like increasing incidence coverage, increasing socioeconomic aspects for all of our patients, particularly those who are marginalized or who are minorities. This is a bigger, national goal and the legislator has to act on it,

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Japanese hospital to evaluate technology used in European trials – Labmate Online

Leading stem cell researchers at Shonan Kamakura General Hospital (SKGH), Japan, are collaborating with regenerative cell therapy developer CellProthera to manufacture autologous endothelial progenitor cells (EPCs) for use in forthcoming clinical trials. Led by world-renowned stem cell expert Takayuki Asahara, MD, PhD, the SKGH research team will use the companys automated manufacturing technology, along with single-use cell culture kits to produce therapies for patients with ischemic and renal diseases.

Professor Asahara, Deputy Director of Shonan Research Institute of Innovative Medicine atSKGH, was the first researcher to isolate EPCs from peripheral blood. EPCs are naturally deployed in the body to repair blood flow after it is restricted (as in ischemic stroke).

CellProtheras StemXpand, which has been in use in European trials to grow patients own cells into a therapeutic dose, will be rigorously tested to meet SKGHs manufacturing specifications and adapted as needed to begin qualification runs for an upcoming clinical trial. After the collaborators confirm consistency and reproducibility both in the manufacturing process and with the previously manufactured product, Prof. Asaharas team will perform validation runs to ready the technologys use for clinical testing.

We are honoured to work with Prof. Asahara given his ground-breaking experience in the regenerative medicine space and think he is the ideal partner to demonstrate the utility of our manufacturing technology beyond our own pipeline, said Matthieu de Kalbermatten, CEO, CellProthera. As a long-time advocate for the use of stem cells for the treatment of ischemic and renal diseases, I am hopeful this collaboration will pave the way for the StemXpand and StemPack to play a pivotal role in the research and development of stem cell treatments across the globe.

Ischemic diseases remain one of the leading causes of death in Japan, with limited treatment options, commented Prof. Asahara. We hand-picked CellProthera for collaboration based in part on how StemXpand, a tried and trusted technology, will help us meet the needs of patients with ischemic diseases through our development of targeted stem cell therapies.

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Japanese hospital to evaluate technology used in European trials - Labmate Online