iPSCs are typically derived by introducing products of specific sets of pluripotency-associated genes, or "reprogramming factors", into a given cell type. The original set of reprogramming factors (also dubbed Yamanaka factors) are the transcription factors Oct4 (Pou5f1), Sox2, cMyc, and Klf4. While this combination is most conventional in producing iPSCs, each of the factors can be functionally replaced by related transcription factors, miRNAs, small molecules, or even non-related genes such as lineage specifiers.
iPSC derivation is typically a slow and inefficient process, taking 12 weeks for mouse cells and 34 weeks for human cells, with efficiencies around 0.010.1%. However, considerable advances have been made in improving the efficiency and the time it takes to obtain iPSCs. Upon introduction of reprogramming factors, cells begin to form colonies that resemble pluripotent stem cells, which can be isolated based on their morphology, conditions that select for their growth, or through expression of surface markers or reporter genes.
Induced pluripotent stem cells were first generated by Shinya Yamanaka's team at Kyoto University, Japan, in 2006. They hypothesized that genes important to embryonic stem cell (ESC) function might be able to induce an embryonic state in adult cells. They chose twenty-four genes previously identified as important in ESCs and used retroviruses to deliver these genes to mouse fibroblasts. The fibroblasts were engineered so that any cells reactivating the ESC-specific gene, Fbx15, could be isolated using antibiotic selection.
Upon delivery of all twenty-four factors, ESC-like colonies emerged that reactivated the Fbx15 reporter and could propagate indefinitely. To identify the genes necessary for reprogramming, the researchers removed one factor at a time from the pool of twenty-four. By this process, they identified four factors, Oct4, Sox2, cMyc, and Klf4, which were each necessary and together sufficient to generate ESC-like colonies under selection for reactivation of Fbx15.
In June 2007, three separate research groups, including that of Yamanaka's, a Harvard/University of California, Los Angeles collaboration, and a group at MIT, published studies that substantially improved on the reprogramming approach, giving rise to iPSCs that were indistinguishable from ESCs. Unlike the first generation of iPSCs, these second generation iPSCs produced viable chimeric mice and contributed to the mouse germline, thereby achieving the 'gold standard' for pluripotent stem cells.
These second-generation iPSCs were derived from mouse fibroblasts by retroviral-mediated expression of the same four transcription factors (Oct4, Sox2, cMyc, Klf4). However, instead of using Fbx15 to select for pluripotent cells, the researchers used Nanog, a gene that is functionally important in ESCs. By using this different strategy, the researchers created iPSCs that were functionally identical to ESCs.
Reprogramming of human cells to iPSCs was reported in November 2006 by two independent research groups: Shinya Yamanaka of Kyoto University, Japan, who pioneered the original iPSC method, and James Thomson of University of Wisconsin-Madison who was the first to derive human embryonic stem cells. With the same principle used in mouse reprogramming, Yamanaka's group successfully transformed human fibroblasts into iPSCs with the same four pivotal genes, Oct4, Sox2, Klf4, and cMyc, using a retroviral system, while Thomson and colleagues used a different set of factors, Oct4, Sox2, Nanog, and Lin28, using a lentiviral system.
Obtaining fibroblasts to produce iPSCs involves a skin biopsy, and there has been a push towards identifying cell types that are more easily accessible. In 2008, iPSCs were derived from human keratinocytes, which could be obtained from a single hair pluck. In 2010, iPSCs were derived from peripheral blood cells, and in 2012, iPSCs were made from renal epithelial cells in the urine.
Other considerations for starting cell type include mutational load (for example, skin cells may harbor more mutations due to UV exposure), time it takes to expand the population of starting cells, and the ability to differentiate into a given cell type.
The generation of iPS cells is crucially dependent on the transcription factors used for the induction.
Oct-3/4 and certain products of the Sox gene family (Sox1, Sox2, Sox3, and Sox15) have been identified as crucial transcriptional regulators involved in the induction process whose absence makes induction impossible. Additional genes, however, including certain members of the Klf family (Klf1, Klf2, Klf4, and Klf5), the Myc family (c-myc, L-myc, and N-myc), Nanog, and LIN28, have been identified to increase the induction efficiency.
Although the methods pioneered by Yamanaka and others have demonstrated that adult cells can be reprogrammed to iPS cells, there are still challenges associated with this technology:
The table on the right summarizes the key strategies and techniques used to develop iPS cells in the first five years after Yamanaka et al.'s 2006 breakthrough. Rows of similar colors represent studies that used similar strategies for reprogramming.
One of the main strategies for avoiding problems (1) and (2) has been to use minute compounds that can mimic the effects of transcription factors. These molecule compounds can compensate for a reprogramming factor that does not effectively target the genome or fails at reprogramming for another reason; thus they raise reprogramming efficiency. They also avoid the problem of genomic integration, which in some cases contributes to tumor genesis. Key studies using such strategy were conducted in 2008. Melton et al. studied the effects of histone deacetylase (HDAC) inhibitor valproic acid. They found that it increased reprogramming efficiency 100-fold (compared to Yamanakas traditional transcription factor method). The researchers proposed that this compound was mimicking the signaling that is usually caused by the transcription factor c-Myc. A similar type of compensation mechanism was proposed to mimic the effects of Sox2. In 2008, Ding et al. used the inhibition of histone methyl transferase (HMT) with BIX-01294 in combination with the activation of calcium channels in the plasma membrane in order to increase reprogramming efficiency. Deng et al. of Beijing University reported in July 2013 that induced pluripotent stem cells can be created without any genetic modification. They used a cocktail of seven small-molecule compounds including DZNep to induce the mouse somatic cells into stem cells which they called CiPS cells with the efficiency at 0.2% comparable to those using standard iPSC production techniques. The CiPS cells were introduced into developing mouse embryos and were found to contribute to all major cells types, proving its pluripotency.
Ding et al. demonstrated an alternative to transcription factor reprogramming through the use of drug-like chemicals. By studying the MET (mesenchymal-epithelial transition) process in which fibroblasts are pushed to a stem-cell like state, Dings group identified two chemicals ALK5 inhibitor SB431412 and MEK (mitogen-activated protein kinase) inhibitor PD0325901 which was found to increase the efficiency of the classical genetic method by 100 fold. Adding a third compound known to be involved in the cell survival pathway, Thiazovivin further increases the efficiency by 200 fold. Using the combination of these three compounds also decreased the reprogramming process of the human fibroblasts from four weeks to two weeks.
In April 2009, it was demonstrated that generation of iPS cells is possible without any genetic alteration of the adult cell: a repeated treatment of the cells with certain proteins channeled into the cells via poly-arginine anchors was sufficient to induce pluripotency. The acronym given for those iPSCs is piPSCs (protein-induced pluripotent stem cells).
Another key strategy for avoiding problems such as tumor genesis and low throughput has been to use alternate forms of vectors: adenovirus, plasmids, and naked DNA and/or protein compounds.
In 2008, Hochedlinger et al. used an adenovirus to transport the requisite four transcription factors into the DNA of skin and liver cells of mice, resulting in cells identical to ESCs. The adenovirus is unique from other vectors like viruses and retroviruses because it does not incorporate any of its own genes into the targeted host and avoids the potential for insertional mutagenesis. In 2009, Freed et al. demonstrated successful reprogramming of human fibroblasts to iPS cells. Another advantage of using adenoviruses is that they only need to present for a brief amount of time in order for effective reprogramming to take place.
Also in 2008, Yamanaka et al. found that they could transfer the four necessary genes with a plasmid. The Yamanaka group successfully reprogrammed mouse cells by transfection with two plasmid constructs carrying the reprogramming factors; the first plasmid expressed c-Myc, while the second expressed the other three factors (Oct4, Klf4, and Sox2). Although the plasmid methods avoid viruses, they still require cancer-promoting genes to accomplish reprogramming. The other main issue with these methods is that they tend to be much less efficient compared to retroviral methods. Furthermore, transfected plasmids have been shown to integrate into the host genome and therefore they still pose the risk of insertional mutagenesis. Because non-retroviral approaches have demonstrated such low efficiency levels, researchers have attempted to effectively rescue the technique with what is known as the PiggyBac Transposon System. Several studies have demonstrated that this system can effectively deliver the key reprogramming factors without leaving footprint mutations in the host cell genome. The PiggyBac Transposon System involves the re-excision of exogenous genes, which eliminates the issue of insertional mutagenesis.
In January 2014, two articles were published claiming that a type of pluripotent stem cell can be generated by subjecting the cells to certain types of stress (bacterial toxin, a low pH of 5.7, or physical squeezing); the resulting cells were called STAP cells, for stimulus-triggered acquisition of pluripotency.
In light of difficulties that other labs had replicating the results of the surprising study, in March 2014, one of the co-authors has called for the articles to be retracted. On 4 June 2014, the lead author, Obokata agreed to retract both the papers  after she was found to have committed research misconduct as concluded in an investigation by RIKEN on 1 April 2014.
MicroRNAs are short RNA molecules that bind to complementary sequences on messenger RNA and block expression of a gene. Measuring variations in microRNA expression in iPS cells can be used to predict their differentiation potential. Addition of microRNAs can also be used to enhance iPS potential. Several mechanisms have been proposed. ES cell-specific microRNA molecules (such as miR-291, miR-294 and miR-295) enhance the efficiency of induced pluripotency by acting downstream of c-Myc.microRNAs can also block expression of repressors of Yamanakas four transcription factors, and there may be additional mechanisms induce reprogramming even in the absence of added exogenous transcription factors.
The task of producing iPS cells continues to be challenging due to the six problems mentioned above. A key tradeoff to overcome is that between efficiency and genomic integration. Most methods that do not rely on the integration of transgenes are inefficient, while those that do rely on the integration of transgenes face the problems of incomplete reprogramming and tumor genesis, although a vast number of techniques and methods have been attempted. Another large set of strategies is to perform a proteomic characterization of iPS cells. Further studies and new strategies should generate optimal solutions to the five main challenges. One approach might attempt to combine the positive attributes of these strategies into an ultimately effective technique for reprogramming cells to iPS cells.
Another approach is the use of iPS cells derived from patients to identify therapeutic drugs able to rescue a phenotype. For instance, iPS cell lines derived from patients affected by ectodermal dysplasia syndrome (EEC), in which the p63 gene is mutated, display abnormal epithelial commitment that could be partially rescued by a small compound
An attractive feature of human iPS cells is the ability to derive them from adult patients to study the cellular basis of human disease. Since iPS cells are self-renewing and pluripotent, they represent a theoretically unlimited source of patient-derived cells which can be turned into any type of cell in the body. This is particularly important because many other types of human cells derived from patients tend to stop growing after a few passages in laboratory culture. iPS cells have been generated for a wide variety of human genetic diseases, including common disorders such as Down syndrome and polycystic kidney disease. In many instances, the patient-derived iPS cells exhibit cellular defects not observed in iPS cells from healthy patients, providing insight into the pathophysiology of the disease. An international collaborated project, StemBANCC, was formed in 2012 to build a collection of iPS cell lines for drug screening for a variety of disease. Managed by the University of Oxford, the effort pooled funds and resources from 10 pharmaceutical companies and 23 universities. The goal is to generate a library of 1,500 iPS cell lines which will be used in early drug testing by providing a simulated human disease environment. Furthermore, combining hiPSC technology and genetically-encoded voltage and calcium indicators provided a large-scale and high-throughput platform for cardiovascular drug safety screening.
A proof-of-concept of using induced pluripotent stem cells (iPSCs) to generate human organ for transplantation was reported by researchers from Japan. Human liver buds (iPSC-LBs) were grown from a mixture of three different kinds of stem cells: hepatocytes (for liver function) coaxed from iPSCs; endothelial stem cells (to form lining of blood vessels) from umbilical cord blood; and mesenchymal stem cells (to form connective tissue). This new approach allows different cell types to self-organize into a complex organ, mimicking the process in fetal development. After growing in vitro for a few days, the liver buds were transplanted into mice where the liver quickly connected with the host blood vessels and continued to grow. Most importantly, it performed regular liver functions including metabolizing drugs and producing liver-specific proteins. Further studies will monitor the longevity of the transplanted organ in the host body (ability to integrate or avoid rejection) and whether it will transform into tumors. Using this method, cells from one mouse could be used to test 1,000 drug compounds to treat liver disease, and reduce animal use by up to 50,000.
Embryonic cord-blood cells were induced into pluripotent stem cells using plasmid DNA. Using cell surface endothelial/pericytic markers CD31 and CD146, researchers identified 'vascular progenitor', the high-quality, multipotent vascular stem cells. After the iPS cells were injected directly into the vitreous of the damaged retina of mice, the stem cells engrafted into the retina, grew and repaired the vascular vessels.
Labelled iPSCs-derived NSCs injected into laboratory animals with brain lesions were shown to migrate to the lesions and some motor function improvement was observed.
Although a pint of donated blood contains about two trillion red blood cells and over 107 million blood donations are collected globally, there is still a critical need for blood for transfusion. In 2014, type O red blood cells were synthesized at the Scottish National Blood Transfusion Service from iPSC. The cells were induced to become a mesoderm and then blood cells and then red blood cells. The final step was to make them eject their nuclei and mature properly. Type O can be transfused into all patients. Human clinical trials were not expected to begin before 2016.
The first human clinical trial using autologous iPSCs was approved by the Japan Ministry Health and was to be conducted in 2014 at the Riken Center for Developmental Biology in Kobe. However the trial was suspended after Japan's new regenerative medicine laws came into effect in November 2015. More specifically, an existing set of guidelines was strengthened to have the force of law (previously mere recommendations). iPSCs derived from skin cells from six patients suffering from wet age-related macular degeneration were reprogrammed to differentiate into retinal pigment epithelial (RPE) cells. The cell sheet would be transplanted into the affected retina where the degenerated RPE tissue was excised. Safety and vision restoration monitoring were to last one to three years.
In March 2017 a team led by Masayo Takahashi completed the first successful transplant of iPS-derived retinal cells from a donor into the eye of a person with advanced macular degeneration. However it was reported that they are now having complications. The benefits of using autologous iPSCs are that there is theoretically no risk of rejection and that it eliminates the need to use embryonic stem cells. However, the iPSCs were derived from another person.
The other multipotent mesenchymal stem cell, when induced into pluripotence, holds great promise to slow down the aging process. Such anti-aging properties were demonstrated in early clinical trials in 2017.
See the original post here:
Induced pluripotent stem cell - Wikipedia
- Century Therapeutics to Present at the 63rd American Society of Hematology Annual Meeting and Host Virtual Research & Development Update - Yahoo... - November 8th, 2021
- BioRestorative Therapies Prices $23 Million Public Offering - GlobeNewswire - November 8th, 2021
- Lab-Growing Everything Might Be The Only Way To Attain A Sustainable World - Intelligent Living - November 8th, 2021
- Probiotics Market to Experience Significant Growth during the Forecast Period 2021-2028 Bolivar Commercial - Bolivar Commercial - November 8th, 2021
- They demonstrate the existence of stem cells in the hippocampus of the human brain - Market Research Telecast - October 28th, 2021
- BioRestorative Therapies Announces Nomination of Two New Members to the Board of Directors - StreetInsider.com - October 28th, 2021
- Akiko Nishiyama Explains the Many Strengths of a Degree in Physiology and Neurobiology - UConn Today - UConn Today - October 28th, 2021
- New stem cell identified by Sanford Burnham Prebys researchers offers hope to people with rare liver disease - Newswise - October 16th, 2021
- The Impact Of Market Restrictions On The US Stem Cell Biomaterials Market - Med Device Online - October 16th, 2021
- College Student and Retired Teacher to Thank Stem Cell Donors They've Never Met for Saving Their Lives During City of Hope's 45th Bone Marrow... - October 16th, 2021
- Phase 2 Clinical Trial Data of NurOwn in Progressive MS Will Be Presented at the 37th Congress of the European Committee for Treatment and Research in... - October 16th, 2021
- Cell therapy strategies for COVID-19: Current approaches and potential applications - Science Advances - August 18th, 2021
- Stem Cell Therapy Market worth $40.3 billion by 2027 Exclusive Report by CoherentMarketInsights - PharmiWeb.com - August 18th, 2021
- Therapeutic Solutions International Reports Superior Neurogenesis Induction in Animal Model of Viral Induced Cognitive Dysfunction Compared to other... - August 18th, 2021
- Atf3 and Rab7b genes drive regeneration in mature cells - Baylor College of Medicine News - August 18th, 2021
- U of T's Medicine by Design helps unite international researchers working to map every human cell - News@UofT - August 18th, 2021
- Mesenchymal Stem Cells Market Witnesses Upward Trend with High Prevalence of Parkinson's Disease The Manomet Current - The Manomet Current - July 22nd, 2021
- BioRestorative Therapies Announces Notice of Allowance for a New Patent Application Related to its Off-the-Shelf ThermoStem Program -... - April 4th, 2021
- Transplant After CD19 CAR T-Cell Therapy Shows Durable Disease Control in Children, Young Adults With B-ALL - Cancer Network - April 4th, 2021
- Stem Cell Assay Market Changing Dynamics Of Competition With Forecast To 2030 The Bisouv Network - The Bisouv Network - April 4th, 2021
- Stem Cell Therapy Market Research Reveals Enhanced Growth During The Forecast Period 2017 2025 FLA News - FLA News - March 8th, 2021
- Adult Stem Cells Market Size, Share, Global Industry Overview, Challenges, Business Overview and Forecast Research Study 2024 (Effect of the COVID-19... - February 17th, 2021
- Be The Match encourages people of color to join bone marrow registry - KING5.com - February 17th, 2021
- Discovery for turning on cell repair in tissues and organs - Monash University - February 17th, 2021
- Manageable Safety Profile Observed in Phase 1 Studies Examining UCART19 for Pediatric and Adult Patients with B-Cell ALL - Cancer Network - February 11th, 2021
- The Very First Signs of an Immune Response Have Been Filmed in a Developing Embryo - ScienceAlert - February 11th, 2021
- JSP191 With Low Dose Irradiation and Fludarabine is Safe and Effective for Patients with MRD+ AML/MDS - Cancer Network - February 9th, 2021
- Creative Bioarray Offers Stem Cell Lines Generation Service for Promoting Scientific Research - Press Release - Digital Journal - February 9th, 2021
- JSP191 With Low Dose Irradiation and Chemotherpy Demonstrates Efficacy and Safety in MRD+ AML/MDS - Targeted Oncology - February 9th, 2021
- Stem Cells Market Value to Reach Around USD 17.79 Bn by 2027 - GlobeNewswire - February 4th, 2021
- Global Adult Stem Cells Market Revenue To Witness Humongous Elevation By 2026 Market Research Store Jumbo News - Jumbo News - February 4th, 2021
- Stem Cell Therapy Market to Score Past US$ 40.3 Billion Valuation by 2027: At a CAGR of 21.1% KSU | The Sentinel Newspaper - KSU | The Sentinel... - February 2nd, 2021
- Reduced Adult Neurogenesis Linked with Alzheimers Disease - The Scientist - February 2nd, 2021
- Regenerative Medicine (Bone and Joint) Market to Score Past US$ 14990.0 Million Valuation by 2027: CMI KSU | The Sentinel Newspaper - KSU | The... - February 2nd, 2021
- Orthopedic Regenerative Medicine Market Size to Witness A Lucrative Growth Over 2020-2027 | Curasan, Inc., Carmell Therapeutics Corporation, Anika... - February 2nd, 2021
- Adult Stem Cells Market Demand, Growth Challenges, Industry Analysis And Forecasts To 2026 | Epistem Ltd.,Globalstem,Mesoblast Ltd.,Brainstorm Cell... - February 2nd, 2021
- ToolGen ties up with 3D bioprinting company to apply induced pluripotent stem cells to gene correction - Aju Business Daily - February 2nd, 2021
- Medicine by Design researchers focus on promoting self-repair of the brain - News@UofT - January 31st, 2021
- Should You Buy Brainstorm Cell Therapeutics Inc (BCLI) Stock on Tuesday? - InvestorsObserver - January 31st, 2021
- Eye stem cell transplant to treat blindness bolsters retinal function in monkeys - FierceBiotech - January 14th, 2021
- Induction of muscle-regenerative multipotent stem cells from human adipocytes by PDGF-AB and 5-azacytidine - Science Advances - January 14th, 2021
- RoosterBio Partners with Sartorius to Advance Cell and Gene Therapy Manufacturing - GlobeNewswire - January 14th, 2021
- Reversing The Aging Clock With Epigenetic Reprogramming - Bio-IT World - January 14th, 2021
- New Models in Organoids Market Open New Vistas in Stem Cell Research for Cancer, Global Valuation to Reach US$ 12.8 Bn by 2030: TMR - PRNewswire - January 12th, 2021
- Health Canada Approves ONUREG (azacitidine tablets), First Maintenance Therapy for Patients in Remission from Acute Myeloid Leukemia - Canada NewsWire - January 12th, 2021
- Stem Cells Market 2020 Research Study including Growth Factors, Types and Application to 2026| Covid-19 Impact - Farming Sector - January 9th, 2021
- The real reason behind goosebumps - Jill Lopez - January 3rd, 2021
- Synthetic lethality across normal tissues is strongly associated with cancer risk, onset, and tumor suppressor specificity - Science Advances - January 3rd, 2021
- New Approaches to the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma - Targeted Oncology - January 3rd, 2021
- CAR T-Cell Therapies Are Set to Expand Into More Hematologic Malignancy Indications - Targeted Oncology - December 26th, 2020
- ElevateBio's HighPassBio Presents on Novel T Cell Receptor Cell Therapy for Leukemia Relapse at 62nd Annual ASH Meeting - Business Wire - December 6th, 2020
- CRISPR and another genetic strategy fix cell defects in two common blood disorders - Science Magazine - December 6th, 2020
- Multiple sclerosis iPS-derived oligodendroglia conserve their properties to functionally interact with axons and glia in vivo - Science Advances - December 6th, 2020
- UCART22 Safe and Active in CD22-Expressing B-Cell ALLs - Targeted Oncology - December 6th, 2020
- Cell Therapy Market Size, Share, Market Research and Industry Forecast Report, 2020-2027 (Includes Business Impact of COVID-19) - Cheshire Media - December 6th, 2020
- Stem Cells Market is Expected to Thrive at Impressive CAGR by 2025 - The Haitian-Caribbean News Network - December 5th, 2020
- Stem Cell Assay to Register Substantial Expansion by 2026| Merck, Thermo Fisher Scientific, GE Healthcare - The Haitian-Caribbean News Network - December 5th, 2020
- Stem Cell Therapy Global Market Report 2020-30: Covid 19 Growth and Change - GlobeNewswire - November 25th, 2020
- Functionally distinct resident macrophage subsets differentially shape responses to infection in the bladder - Science Advances - November 25th, 2020
- BioRestorative Therapies Emerges from Chapter 11 Reorganization Other OTC:BRTX - GlobeNewswire - November 20th, 2020
- Jakafi and Dacogen May Improve Overall Survival in Patients with MPN - Curetoday.com - November 20th, 2020
- BRTX-100; the Story of BioRestorative Therapies Inc (OTCMKTS: BRTX) - MicroCap Daily - November 20th, 2020
- As California Passes Prop 14, What Is Stem Cell Research and Why Is It Controversial? - Newsweek - November 16th, 2020
- Organoids mimic the early development of the heart in mouse embryos - BioNews - November 16th, 2020
- Human mesenchymal stromal cells do not express ACE2 and TMPRSS2 and are not permissive to SARS-CoV-2 infection - DocWire News - November 16th, 2020
- Cynata Therapeutics (ASX:CYP) begins phase three osteoarthritis trial - The Market Herald - November 16th, 2020
- $ 30.1 billion Worth Cell Expansion Market, Led by Thermo Fisher Scientific Inc, Becton, Dickinson and Company, Terumo BCT and Others. re:Jerusalem -... - November 3rd, 2020
- Impact of COVID-19 on Advanced Wound Care Management Market : Implications on Business Strategies, Countermeasures, Economic Impact - The Think... - November 1st, 2020
- Stem Cells Market 2020 Is Growing with Highest Size, Share of Top Key Players in the Industry and Forecast Survey Till 2024 - Zenit News - October 30th, 2020
- Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease - DocWire News - October 30th, 2020
- JadiCell Stem Cells Licensed by Therapeutic Solutions International for Brain Injury Significantly Increased Survival of COVID-19 Patients in Double... - October 29th, 2020
- Impact Of Covid 19 On Adult Stem Cells Market 2020 Industry Challenges, Business Overview And Forecast Research Study 2026 - PRnews Leader - October 29th, 2020
- APstem Therapeutics Announces Successful FDA INTERACT Meeting Regarding AP-Skin-01, an Off-the-Shelf Allogeneic Stem Cell Product for the Treatment of... - October 29th, 2020
- Why Small Businesses Matter in Wilton (Reimagined): Interventional Orthopedics Connecticut - HamletHub - October 29th, 2020
- Covid-19 Impact On Orthopedic Regenerative Medicine Market 2020 Future Development, Manufacturers, Trends, Share, Size And Forecast to 2027 |... - October 29th, 2020
- Cell Expansion Market a comprehensive study by key players- Thermo Fisher Scientific, Inc, Becton, Dickinson and Company, Terumo BCT, Merck KGaA and... - October 24th, 2020
- Genmab Announces IFM, HOVON and Janssen Achieve Positive Topline Results in Second Part of Phase 3 CASSIOPEIA Study of Daratumumab in Multiple Myeloma... - October 24th, 2020
- What Is the Role of Allogeneic-SCT in Adult Acute Lymphoblastic Leukemia in the Era of Targeted Therapies? - Targeted Oncology - October 21st, 2020
- Cell Therapy Market Size, Share, Market Research and Industry Forecast Report, 2020-2027 (Includes Business Impact of COVID-19) - Eurowire - October 17th, 2020
- Global Stem Cell Therapy Market (Covid-19 updated report), Trends, Top Manufacturers, Exponential Growth and Forecast 2020 to 2027 By Reportspedia -... - October 17th, 2020