A U.S. study has shown for the first time that enhancing signals from the nociceptive nervous system could provide new approaches to improve the collection of hematopoietic stem cells (HSCs) for treating cancers of the blood and bone marrow, the authors reported in the December 23, 2020, edition of Nature.
The findings may help cancer treatments, as "in a meaningful fraction of leukemia, multiple myeloma and lymphoma patients, particularly those who have received anticancer treatment, the HSC mobilization yield can be insufficient," said study leader Paul Frenette.
"Therefore, more efficient HSC mobilization methods would allow the harvest of sufficient HSCs for life-saving transplantation," said Frenette, a professor and director of the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Albert Einstein College of Medicine in New York.
HSCs characteristically migrate to different hematopoietic sites during embryonic development and continue to be released from the adult bone marrow.
Most hematopoiesis occurs in the bone marrow, where different types of blood cells are derived from limited numbers of HSCs, which are multipotent and capable of extensive renewal.
The HSC migratory properties have facilitated their collection from the blood and transplantation as regenerative cancer treatment, although the mechanisms by which HSCs migrate out of the bone marrow remain largely unknown.
In tissues exposed to the external environment, such as the skin, lung and gut, nociceptors enable the rapid detection of external insults, including pain, cold or heat, in order to avoid organ damage.
Nociceptor sensory neurons detect these harmful stimuli and can regulate the immune response to them by releasing neurotransmitters and other regulatory molecules.
However, other than for pain perception, the role of nociceptors in a deep tissue, such as the bone marrow, is poorly understood.
In bone marrow, HSCs are found in specialized microenvironments or niches, which are complex regulatory environments influenced by multiple cellular constituents, including nerves.
Although sympathetic nerves are known to regulate the HSC niche, the role of nociceptive neurons in the bone marrow in this regard remains unclear.
"We have previously shown that nerves from the sympathetic nervous system promoted HSC mobilization in bone marrow, so we were curious to see whether nociceptive neurons might also be involved," Frenette told BioWorld Science.
In their new Nature study, the Frenette and his team showed that nociceptive neurons are required for HSC mobilization and that they interact with sympathetic nerves to maintain HSCs in the bone marrow.
Notably, nociceptor neurons were demonstrated to drive granulocyte colony-stimulating factor (G-CSF)-induced HSC mobilization via secretion of calcitonin gene-related peptide (CGRP).
"Our findings may lead to more efficient mobilization methods in [blood and bone marrow cancer] patients in whom existing methods are insufficient," Frenette said.
For example, "we have shown that the CGRP pathway synergizes with G-CSF and plerixafor [(Mozobil, Genzyme), an immunostimulant used to mobilize HSCs into the bloodstream in cancer patients]." Unlike sympathetic nerves, which regulate HSCs indirectly via the bone marrow niche, CGRP was shown to act directly on HSCs via receptor activity modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor to promote HSC egress via Galphas/adenyl cyclase/cAMP signaling pathway activation.
This research identifies potential treatment targets for boosting HSC mobilization, since "we have shown that increasing the downstream signaling of the CGRP receptor RAMP1, by increasing cyclic AMP can enhance HSC mobilization," said Frenette.
Importantly, the Einstein researchers then showed that ingestion of food containing capsaicin, a natural component of chili peppers that can trigger the activation of nociceptive neurons, significantly enhanced HSC mobilization in mice.
"Capsaicin tablets are currently sold over-the-counter to 'help support cardiovascular and digestive function' at higher doses than that predicted by our studies in mice for stimulating HSC mobilization in humans," said Frenette.
"These relatively low concentrations of capsaicin have biological effects without seemingly causing obvious pain," he said.
Collectively, these findings therefore suggest that targeting the nociceptive nervous system could represent a novel strategy by which to improve the yield of HSCs for stem cell-based therapies. (Gao, X. et al. Nature 2020, Advanced publication).
Read more:
Nociceptive neurons shown to boost hematopoiesis | 2020-12-28 - BioWorld Online
- Mouth Sores from Chemo: Symptoms, Causes, and Treatments - Healthline - February 19th, 2021
- ThermoGenesis Holdings Begins a Year of Celebration of its 35th Anniversary in the Cell Banking and Cell Therapy Industry - PRNewswire - February 19th, 2021
- Meet the women hoping to recruit more stem cells donors from Black communities - CTV News - February 19th, 2021
- CAR T-Cell Therapy Carves Out a Role in Multiple Myeloma - OncLive - February 19th, 2021
- AI project to power the future of stem cell manufacturing - TechCentral.ie - February 17th, 2021
- Promising Results for Stem Cell Treatment of Degenerative ... - February 14th, 2021
- Stem Cell Therapy for Heart Disease - Cleveland Clinic - February 14th, 2021
- Stem Cell Therapy for Stroke Recovery | University of ... - February 14th, 2021
- Stem Cell Treatment: Future of Modern Medicine | Science Times - February 14th, 2021
- Researchers may have found a miracle cure for baldness - BGR - February 14th, 2021
- Types of leukemia: Prevalence, treatment options, and prognosis - Medical News Today - February 14th, 2021
- Jasper Therapeutics Announces Launch of New Clinical Trial with National Heart, Lung, and Blood Institute to Evaluate JSP191 in Sickle Cell Disease -... - February 14th, 2021
- Global Stem Cell Therapy Market Set to Reach USD 214.5 Million by 2024 - The Courier - February 14th, 2021
- Keep it Flowing: Combating COVID-19 Blood Shortages in Cancer Treatment - Curetoday.com - February 14th, 2021
- Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease - Science - February 14th, 2021
- AlloVir Research Presented at the 2021 Transplantation & Cellular Therapy Meeting Digital Experience - Business Wire - February 14th, 2021
- Orchard Therapeutics talks the benefits of HSC therapy - BioProcess Insider - February 14th, 2021
- Protein Discovery in the Development of New Hearing Hair Cells Could Lead to Treatments for Hearing Loss - SciTechDaily - February 7th, 2021
- Stem cells efficacy confirmed in treating ototoxic hearing loss - Korea Biomedical Review - February 4th, 2021
- Groundbreaking Trial Shows Umbilical-Cord Derived Mesenchymal Stem Cell Infusions Save Lives of Sickest COVID-19 Patients - HospiMedica - January 22nd, 2021
- Massive Growth in Canine Stem Cell Therapy Market Set to Witness Huge Growth by 2027| VETSTEM BIOPHARMA, Cell Therapy Sciences, Regeneus, Aratana... - January 22nd, 2021
- Autologous stem cell transplantation versus bortezomib for the first line treatment of systemic light chain amyloidosis in the UK - DocWire News - January 22nd, 2021
- Promising Steps Toward Retinal Cell Transplants to Fight Blindness - HealthDay News - January 22nd, 2021
- Hemostemix Announces the Bread Contract with the Department of Foreign Affairs, Trade & Development Canada - InvestorIntel - January 22nd, 2021
- Trending News on Targeted Oncology, Week of January 22, 2021 - Targeted Oncology - January 22nd, 2021
- Stem Cell Therapy Market Size, Growth Opportunities, Trends, Key Players and Forecast to 2027 - The Courier - January 22nd, 2021
- Time To Book Profit In Fate Therapeutics Stock After A 5x Rally? - Forbes - January 22nd, 2021
- Reid Merryman, MD, on Study Findings Investigating Prognostic Value of ctDNA for Patients with DLBCL - Cancer Network - January 22nd, 2021
- Co-founder Thomas Smeenk on the benefits of Hemostemix autologous stem cell therapy - InvestorIntel - January 12th, 2021
- Covid-19 Impact On Stem Cell Therapy Market 2020 Huge Potential in Future Growth by 2027 | Magellan, Medipost Co., Ltd, Osiris Therapeutics, Inc.,... - January 12th, 2021
- Adipose Derived Stem Cell Therapy Market Analysis and Forecast, 2020-2026 Coherent Market Insights | BioRestorative Therapies, Inc., Celltex... - January 12th, 2021
- New COVID-19 Treatment Uses Stem Cells - Freethink - January 12th, 2021
- Creative Medical Technology Holdings Files Investigational New Drug Application (IND) with FDA for Treatment of Stroke using ImmCelz Regenerative... - January 12th, 2021
- Global Cell Freezing Media for Cell Therapy Market 2020 Dynamics Analysis, Size Witness Growth Acceleration During 2025 - KSU | The Sentinel Newspaper - January 12th, 2021
- Gamida Cell to Present Full Data from Phase 3 Study of Omidubicel at TCT, the Combined Transplantation and Cellular Therapy Meetings of ASTCT and... - January 12th, 2021
- Cate Dyer of StemExpress is Named Businesswoman of the Year! - PRNewswire - January 12th, 2021
- Adocia Files Patent on a Hydrogel Scaffold for Cell Therapy in the Treatment of Type 1 Diabetes - Business Wire - January 12th, 2021
- Gene Therapy Market Estimated to Record Highest CAGR by 2024 - KSU | The Sentinel Newspaper - January 12th, 2021
- Stem cell treatment corrects skull shape and restores brain function in mouse model of childhood disorder - National Institutes of Health - January 9th, 2021
- Doctors Make Medical Breakthrough In Treating Severe Cases Of COVID - CBS New York - January 9th, 2021
- Global Stem Cell Therapy Market Report 2020: Market to Recover and Reach $14.76 Billion in 2023 at a CAGR of 19.62% - Forecast to 2030 - Yahoo Finance - January 9th, 2021
- Engineered stem cells that evade immune detection could boost cell therapy and I-O - FierceBiotech - January 9th, 2021
- BENEV Announces Investigative Report on Combination Treatment with Human Adipose Tissue Stem Cell- derived Exosomes and Fractional CO2 Laser for Acne... - January 9th, 2021
- Four promising COVID-19 therapies being tested at nearby UVA - Rappahannock News - January 9th, 2021
- MCL Landscape Adapts to Changes After CAR T-Cell Therapy Approval - OncLive - January 9th, 2021
- Regenerative Medicine Market to Reach Valuation US$ 23.7 Bn by 2027 - GlobeNewswire - January 9th, 2021
- Unlocking The Unlimited Potential Of Stem Cells - CodeBlue - January 9th, 2021
- Stem Cell Treatment Proving Highly Successful In Treating Most Severe Cases Of COVID - Yahoo News - January 9th, 2021
- Factor Bioscience spins out a new cell therapy player with eyes on the clinic within 2 years - Endpoints News - January 9th, 2021
- Comparison of the efficiency, safety, and survival outcomes in two stem cell mobilization regimens with cyclophosphamide plus G-CSF or G-CSF alone in... - January 9th, 2021
- Top 10 ALS Stories of 2020 - ALS News Today - January 9th, 2021
- Celularity and GX Acquisition Corp. Announce Merger Agreement to Create a Publicly Listed Leader in Allogeneic Cellular Therapy - BioSpace - January 9th, 2021
- Results Show Promising Efficacy in MCL With Next-Generation BTK Inhibitor LOXO-305 - Cancer Network - January 9th, 2021
- BlueRock Therapeutics in Collaboration with Memorial Sloan Kettering Cancer Center Receives IND Clearance for DA01 in Parkinson's Disease - BioSpace - January 9th, 2021
- Stem Cell Therapy Market Size, Share & Trends Analysis Report By Product Types, And Applications Forecast To 2026 - Farming Sector - January 5th, 2021
- Stem Cell Therapy Market by Treatment,Application,End Users and Geography Forecast To 2027 - LionLowdown - January 5th, 2021
- Stem Cell Therapy Market Analysis, COVID-19 Impact,Outlook, Opportunities, Size, Share Forecast and Supply Demand 2021-2025 - Farming Sector - January 5th, 2021
- AGC Biologics Confirms Cell and Gene Therapy Commercial Expertise as Manufacturer of Orchard Therapeutics' Newly Approved Libmeldy - PRNewswire - January 5th, 2021
- Forge Biologics Announces FDA Clearance of Investigational New Drug Application for Phase 1/2 Clinical Trial (RESKUE) of FBX-101 Gene Therapy for... - January 5th, 2021
- MorphoSys and Incyte Announce the Acceptance of the Swissmedic Marketing Authorization Application f - PharmiWeb.com - January 5th, 2021
- Healthcare resource utilization and costs among patients with relapsed and/or refractory multiple myeloma treated with proteasome inhibitors in... - January 5th, 2021
- Global Circulating Tumor Cells and Cancer Stem Cells Market To Reach A New Threshold of Growth By 2026 - The Courier - January 5th, 2021
- Catheters Market: Europe and North America Emerge as Leading Regional Market with Well-established Healthcare Infrastructure - BioSpace - January 5th, 2021
- The Worldwide Cell Isolation/Cell Separation Industry is Expected to Grow at a CAGR of 16.8% Between 2020 to 2025 - PRNewswire - January 5th, 2021
- Near-infrared oxidative phosphorylation inhibitor integrates acute myeloid leukemiatargeted imaging and therapy - Science Advances - January 5th, 2021
- Global Cell Therapy Market Report 2020: Market to Recover in 2023 - PRNewswire - January 3rd, 2021
- Lonza's Cocoon will soon make dozens of stem cell therapies all at once - Innovation Origins - January 3rd, 2021
- Induced Pluripotent Stem Cell Derived Human Lung Organoids to Map and Treat the SARS-CoV2 Infections In Vitro - DocWire News - January 3rd, 2021
- Creative Medical Technology Holdings Announces Patent filing based on Preclinical Data in Model of Heart Attack using ImmCelz Regenerative... - January 3rd, 2021
- Haywards Heath carer trying to raise funds for MS treatment - The Argus - January 3rd, 2021
- Chronic graft-versus-host disease in children and adolescents with thalassemia after hematopoietic stem cell transplantation - DocWire News - January 3rd, 2021
- COVID-19-positive cancer patients undergoing active anticancer treatment: An analysis of clinical features and outcomes - DocWire News - January 3rd, 2021
- Cell Therapy Market 2020-2026 by Growth, Demand and Upcoming Business Opportunities - Farming Sector - January 3rd, 2021
- Rheumatoid Arthritis Stem Cell Therapy Market Latest Trends and Future Growth Study by 2029 - Farming Sector - December 31st, 2020
- Creative Medical Technology Holdings Announces Reversion of Liver Failure Using ImmCelz Personalized Cellular Immunotherapy in Preclinical Model -... - December 31st, 2020
- Impacts of COVID 19 on Stem Cell Therapy Market 2020 Size, Demand, Opportunities & Forecast To 2026 - Factory Gate - December 31st, 2020
- Efficacy and safety of mesenchymal stem cells for the treatment of patients infected with COVID-19: a systematic review and meta-analysis protocol -... - December 31st, 2020
- Global Stem Cell Therapy Market Industry 2021 In-depth Market Analysis and Recent Developments, Share, Revenue and Forecast 2025 | Anterogen Co. Inc.... - December 31st, 2020
- Stem Cell Therapy Market 2020: Demand Analysis, Key Players, Trends, Sales, Supply, Deployment Model, Segments, Organization Size, Production, Revenue... - December 28th, 2020
- Stem Cell Therapy Market (COVID-19 Analysis) 2020-2025 Is Booming Worldwide with Comprehensive Study Explores Huge Revenue Scope in Future - Farming... - December 28th, 2020