During development, unspecialised cells (stem cells) contribute to the formation of the body. Responding to the various cues of the microenvironment, stem cells migrate and differentiate into various cell types with different and specific functions, forming organs and tissues. In addition to constituting the building blocks of the body, a few stem cells remain in most of our organs and are recruited later in life to repair tissues and regain organ function after acute injury. Capitalising on the potential of endogenous stem cells to specialise and to regenerate tissues, stem cells have been considered as a tool for the treatment of various pathologies including genetic diseases where organ function is im-paired because of a genetic mutation.
Osteogenesis imperfecta, also called brittle bone disease, is a genetic disease that manifests before birth by fragile bones that break easily in response to a genetic mutation in the genes coding for collagen, which is produced by bone-forming cells (osteoblasts). As collagen is the most important constituent of bones and skin, the presence of mutation results in abnormal or insufficient collagen, which translates to reduced bone mass and strength.
Human mesenchymal stem cells (MSCs) are found in tissues of mesenchymal/ stromal origin such as bone marrow. Stem cells with similar characteristics as bone marrow MSCs have also been found in other tissues, at various stages of gestation. Compared to adult MSCs, MSCs found in fetal tissues, also called human fetal MSCs (hfMSCs) present several advantageous characteristics, including higher cell division speed, superior ability to differentiate, and greater tissue repair potential. MSCs can be isolated from healthy donors, expanded in vitro to high numbers, and subsequently frozen at a very low temperature. Capitalising on their ability to differentiate in various cell lineages, MSCs can then be thawed and used for clinical purposes in regenerative medicine.
Because bone fragility in osteogenesis imperfecta is due to osteoblast not producing the correct amount or form of collagen, it has been hypothesised that transplanting healthy osteoblasts at an early stage of skeletal development (during fetal life or at birth) would reinforce bones by creating a chimeric skeleton composed of osteoblasts carrying the mutation and some not carrying it. However, we have shown that it was preferable to transplant stem cells than osteoblasts because once differentiated, cells lose their ability to migrate to various organs in the body and engraft. Instead, the proposed strategy has been to transplant hfMSC during early life (pre-or post-natal). This presents several advantages. First, the injection of healthy cells occurs at a time when the disease has been diagnosed by the damages to the bones is not yet advanced as the skeleton will be growing for several years. Second, transplantation is a small size recipient that requires less cells. Finally, transplantation can occur at a time when the immune system is so immature that it will not reject the cells that have been transplanted.
We have compared various sources of hfMSC and found that first-trimester blood hfMSC are more osteogenic than their liver counterparts. 1 Human fetal stem cells with similarly high osteogenic potential can also be isolated from the amniotic fluid that surrounds babies in the womb during the second trimester of pregnancy, and amniotic fluid stem cells (AFSCs) are now considered as a source of choice for perinatal cell therapy. The rationale behind hfMSC transplantation is that donor cells are going to survive in the host, migrate to the skeleton where they will differentiate into osteoblasts under the pressure of the local microenvironment and produce healthy collagen. Collagen of donor origin may combine with collagen produced by the host osteoblasts to produce a chimeric bone matrix. We have shown that prenatal or neonatal transplantation of hfMSCs or AFSCs resulted in a two-third reduction in long bone fracture rate and a marked improvement in bone structural and mechanical properties. 2-4
However, several difficulties remain before such an approach can be routinely used in the clinic. First, transplanted stem cells are isolated from the tissues of fetal donors. These primary cells need to be expanded to large numbers in the laboratory to obtain enough cells for transplantation. However, during this lengthy process, stem cells age and progressively start to divide at a slower rate, and lose their ability to differentiate and to repair tissues. As a result, new primary cells need to be isolated from other donors, characterised and expanded in vitro. Consequently, there is high variability between different samples, which creates a hurdle to overcome in order to standardise therapeutic treatments.
One solution is to use human pluripotent stem cells, which have the potential to differentiate into all the cell types of the body, including MSCs, and do not senesce during in vitro expansion. Pluripotent stem cells-derived MSCs (iMSCs) can subsequently be used for perinatal cell therapy for osteogenesis imperfecta as they can readily differentiate into osteoblasts. As pluripotent stem cells escape ageing, the strategy of using iMSCs in replacement of primary hfMSCs enables to standardise treatment therapeutics for clinical applications.
An additional innovative approach for the treatment of osteogenesis imperfecta is the ability to correct genetic mutations using genetic scissors to excise specific sections of DNA. As a result, it is possible to develop personalised stem cell therapy, where somatic cells from patients are isolated from their urine, rejuvenated in vitro to become pluripotent, genetically manipulated to remove the mutation causing osteogenesis imperfecta, and differentiated into iMSCs before being transplanted. Such an approach represents the advantages of standardising treatment.
Research into the mechanisms of action of donor MSCs has revealed that only a few cells engraft in bones and even though these cells differentiate into osteoblasts, it is very unlikely that their sole effect is to contribute to the production of the healthy bone extracellular matrix. Instead, evidence strongly suggests that donor MSCs contribute to improving the quality of the skeleton by modifying the behaviour of the host osteoblasts. Even though the primary effect of the mutation causing osteogenesis imperfecta is the production of abnormal collagen, the knock-on effects of the mutations are a dysfunction of osteoblasts, which become unable to fully differentiate into mature osteo-blasts. As a result, immature osteo-blasts produce abnormal amounts of minerals, which contributes to further fragilise the bone extracellular matrix, because they give strength to the organic matrix composed of collagen fibres. We have shown that donor MSCs contribute to stimulate host osteoblasts to mature, such that the bone extracellular matrix has better quality and becomes stronger.
Such approaches could be used for the treatment of other skeletal dysplasias to develop personalised medicine to improve skeletal health.
References
Please note: This is a commercial profile
2019. This work is licensed underCC-BY-NC-ND.
Editor's Recommended Articles
The rest is here:
Stem cell therapy to treat brittle bone disease - Open Access Government
- Biology of stem cells: an overview - PMC - National Center for ... - March 26th, 2024
- Iron Limitation Preserves Youthfulness of Blood Stem Cells - Mirage News - March 13th, 2024
- Mini organs grown from stem cells of unborn babies for the first time in breakthrough - The Mirror - March 9th, 2024
- The Effect of Short-Term NAD3 Supplementation on Circulating Adult Stem Cells in Healthy Individuals Aged 40-70 ... - Cureus - March 7th, 2024
- University of Liverpool Spin-Out Emerges, Pioneering Novel Adult Stem Cell-Based Therapies - India Education Diary - March 7th, 2024
- Scientists have used cells from fluid drawn during pregnancy to grow mini lungs and other organs - Yahoo News Canada - March 6th, 2024
- Japan approves new stem cell-based Alzheimer's therapy By Proactive Investors - Investing.com Australia - January 20th, 2024
- Cyberstalking pits Harvard professor against PubPeer Retraction ... - Retraction Watch - December 5th, 2023
- 10 functional health predictions for 2024, according to a doctor and ... - 1330 WFIN - December 5th, 2023
- See the Brain Like Never Before in This Gorgeous Art - Scientific American - December 5th, 2023
- Geron Announces Publication in The Lancet of Results from the ... - BioSpace - December 5th, 2023
- Stem cell injections could be the key to curing MS - Freethink - December 3rd, 2023
- Jaypirca (pirtobrutinib) Now Approved by U.S. FDA for the ... - Investors | Eli Lilly and Company - December 3rd, 2023
- Comparative Efficacy and Safety of Four JAK Inhibitors for ... - HealthDay - December 3rd, 2023
- City lights up for Francis on Anthony Nolan's birthday - Liverpool Express - December 3rd, 2023
- NOT-AR-23-022: Request for Information on Themes for the NIAMS ... - National Institutes of Health (.gov) - December 3rd, 2023
- December 2023: Intramural Papers of the Month - Environmental Factor Newsletter - December 1st, 2023
- CNA Explains: What is cord blood banking and why do parents do it? - CNA - December 1st, 2023
- Regulation of myogenesis and adipogenesis by the electromagnetic ... - Nature.com - December 1st, 2023
- The effects of vitamin K on bone health - News-Medical.Net - December 1st, 2023
- Dr Hurwitz on Ongoing Investigations of the Use of CAR T-Cell ... - OncLive - December 1st, 2023
- Mitophagy in human health, ageing and disease - Nature.com - December 1st, 2023
- Adult Stem Cells - Stem Cells and the Future of Regenerative Medicine ... - November 29th, 2023
- Navigating The Regulatory Landscape Of Longevity Health Products ... - Mondaq News Alerts - November 29th, 2023
- MS breakthrough could lead to treatments that halt disease's ... - inews - November 29th, 2023
- Reprogramming tissue mechanically to promote wound healing - Phys.org - November 29th, 2023
- Latest Advances in Arthritis Diagnosis and Treatment at American ... - HealthDay - November 29th, 2023
- Sex-associated differences in frequencies and prognostic impact of ... - Nature.com - November 29th, 2023
- Hematologists Dive into the Current Treatment Landscape - OncLive - November 29th, 2023
- Team discovers protein crucial for B cell differentiation and antibodies - Phys.org - November 29th, 2023
- Science Talk - I survived cancer as a child and now I'm working to ... - The Institute of Cancer Research - November 29th, 2023
- First Edition: Nov. 29, 2023 - KFF Health News - November 29th, 2023
- Symptoms: Unilateral Hearing Loss and Tinnitus : The Hearing Journal - LWW Journals - November 29th, 2023
- Mitigation of sepsis-induced acute lung injury by BMSCs | IJN - Dove Medical Press - November 29th, 2023
- A Case of a Constricted Vessel: The Impact of Acute Myeloid ... - Cureus - November 29th, 2023
- Mum brushed off fatigue after having baby but fall sparked deadly diagnosis - The Mirror - November 29th, 2023
- How heritable is the epigenome? - Drug Discovery News - November 29th, 2023
- The Blueprint of Regeneration: Scientists Discover How to Turn Stem Cells Fate - Revyuh - November 27th, 2023
- BrainStorm Cell Therapeutics Announces In-Person Meeting with ... - Marketscreener.com - November 27th, 2023
- Stem Cell Therapy Developed in Korea Begins Treatment for ... - PharmiWeb.com - November 25th, 2023
- COVID-19 Pandemic's Adverse Effect on Bone Health in Young ... - HealthDay - November 25th, 2023
- Sickle cell breakthrough - The Indian Express - November 25th, 2023
- Wall thickness analysis method for judging the degree of lower ... - Nature.com - November 25th, 2023
- Century Therapeutics to Present at the Piper Sandler 35th Annual Healthcare Conference - Yahoo Finance - November 23rd, 2023
- Disease Transmission and Diagnosis of Zika Virus - Cureus - November 23rd, 2023
- Gene-editing therapy for sickle cell earns conditional approval in UK - Sickle Cell Disease News - November 23rd, 2023
- Stem Cell Therapy Developed in Korea Begins Treatment for ... - Newswire - November 21st, 2023
- Efficacy of ADSC-CM in Patients with Telogen Effluvium | SCCAA - Dove Medical Press - November 21st, 2023
- BrainStorm Cell Therapeutics Announces In-Person Meeting with ... - PR Newswire - November 21st, 2023
- The Impact of CAR T Cell Therapy on Managing R/R LBCL - OncLive - November 21st, 2023
- Mansour bin Zayed witnesses inauguration of ADSCC Bone Marrow Transplant & Cellular Therapy Congress 2023 - ZAWYA - November 21st, 2023
- Listeria: Who is most susceptible? What are the Symptoms? What ... - Food Poison Journal - November 21st, 2023
- Scope Of Issued Patents May Be Limited By Prosecution Estoppel ... - Mondaq News Alerts - November 21st, 2023
- Qrons Announces the Addition of Professor Shiri Navon-Venezia to ... - StreetInsider.com - November 21st, 2023
- Financially strapped Athersys raises $10.4M - cleveland.com - November 19th, 2023
- From the India Today archives (2010) | How stem cells can save your life - India Today - November 19th, 2023
- Inactivation of the tumor suppressor gene Apc synergizes with H ... - Science - November 19th, 2023
- The Origins of Multiple Myeloma and Why it Matters - HealthTree For AML - Acute Myeloid Leukemia - November 19th, 2023
- Treatment Considerations With TROP2-Targeted Therapy - OncLive - November 19th, 2023
- Athersys narrows loss, raises $10.4 million during third quarter to ... - The Business Journals - November 17th, 2023
- Who was Dolly the Sheep and what happened to her? The story of ... - BBC Countryfile Magazine - November 17th, 2023
- UK first to approve CRISPR treatment for diseases: what you need to ... - Nature.com - November 17th, 2023
- 1st sickle cell patient to be given therapy restoring fetal hemoglobin - Sickle Cell Disease News - November 15th, 2023
- Century Therapeutics Reports Third Quarter 2023 Financial Results and Provides Business Updates - Century - Benzinga - November 13th, 2023
- Century Therapeutics Appoints Brent Pfeiffenberger, Pharm.D., MBA, as Chief Executive Officer - Yahoo Finance - November 11th, 2023
- Century Therapeutics and FUJIFILM Cellular Dynamics Announce Licenses for the Development and Commercialization of iPSC-Derived Cell Therapies in... - November 11th, 2023
- AAO 2023: Paul Runge and his ROP treatments in the Ukraine - Modern Retina - November 11th, 2023
- The Evolutionary Reasons We Are Drawn To Horror Movies and ... - Slashdot - November 11th, 2023
- Century Therapeutics Reports Third Quarter 2023 Financial Results ... - GlobeNewswire - November 11th, 2023
- Century Therapeutics Reports Third Quarter 2023 Financial Results ... - StreetInsider.com - November 9th, 2023
- NYU Langone Health Performs World's First Whole-Eye & Partial ... - NYU Langone Health - November 9th, 2023
- BrainStorm to Announce Third Quarter 2023 Financial Results and ... - BioSpace - November 9th, 2023
- Can we cut cost and pain of IVF? Start-up CEO tries out own ... - Genetic Literacy Project - November 9th, 2023
- Jasper Therapeutics Reports Third Quarter 2023 Financial Results ... - BioSpace - November 9th, 2023
- Impaired neural stress resistance and loss of REST in bipolar ... - Nature.com - November 9th, 2023
- Functional genomics and systems biology in human neuroscience - Nature.com - November 9th, 2023
- Trial launched to test CAR T-cell therapy in dogs diagnosed with ... - EurekAlert - November 9th, 2023
- The-Gut's-Lasting-Impact-on-Severe-COVID-19-Immune-Response - Infectious Disease Special Edition - November 9th, 2023
- Emerging Cure for Sickle Cell on its Way to FDA Approval, Carries ... - Dallasweekly - November 7th, 2023
- The science works, but will we pay for it? - Irish Medical Times - November 7th, 2023
Recent Comments