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A Brief Overview of Global Trends in MSC-Based Cell Therapy.

ABSTRACT: Human mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are important adult stem cells for regenerative medicine, largely due to their regenerative characteristics such as self-renewal, secretion of trophic factors, and the capability of inducing mesenchymal cell lineages. MSCs also possess homing and trophic properties modulating immune system, influencing microenvironment around damaged tissues and enhancing tissue repair, thus offering a broad perspective in cell-based therapies. Therefore, it is not surprising that MSCs have been the broadly used adult stem cells in clinical trials. To gain better insights into the current applications of MSCs in clinical applications, we perform a comprehensive review of reported data of MSCs clinical trials conducted globally. We summarize the biological effects and mechanisms of action of MSCs, elucidating recent clinical trials phases and findings, highlighting therapeutic effects of MSCs in several representative diseases, including neurological, musculoskeletal diseases and most recent Coronavirus infectious disease. Finally, we also highlight the challenges faced by many clinical trials and propose potential solutions to streamline the use of MSCs in routine clinical applications and regenerative medicine.

SUBMITTER: Jovic D

PROVIDER: S-EPMC8958818 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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A Brief Overview of Global Trends in MSC-Based Cell Therapy.

Jovic Dragomirka D Yu Yingjia Y Wang Dan D Wang Kuixing K Li Hanbo H Xu Fengping F Liu Chenglong C Liu Junnian J Luo Yonglun Y

Stem cell reviews and reports 20220328 5

Human mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are important adult stem cells for regenerative medicine, largely due to their regenerative characteristics such as self-renewal, secretion of trophic factors, and the capability of inducing mesenchymal cell lineages. MSCs also possess homing and trophic properties modulating immune system, influencing microenvironment around damaged tissues and enhancing tissue repair, thus offering a broa ...[more]

PMID: 35344199

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Project description:BackgroundMesenchymal stromal cells (MSC) demonstrate innate and regulatory immunologic functions and have been widely explored for cell therapy applications. Mechanisms by which MSCs achieve therapeutic effects are theorized, though appropriate dosing and duration of these mechanisms in vivo warrant deeper investigation. One, rapid immunosuppressive function of MSCs is through ectoenzyme expression of CD73 and CD39 which cooperatively hydrolyze inflammatory, extracellular adenosine triphosphate (ATP) to anti-inflammatory adenosine. Extracellular ATP has a key role in autoimmune and inflammatory diseases, which administered MSCs have the potential to modulate in a timescale that is befitting of shorter acting therapeutic function.MethodsIn vitro experiments were performed to determine the hydrolysis rates of ATP by MSCs. Through kinetic modeling from experimental results, the rate at which a single cell can metabolize ATP was determined. Based on these rates, the ability of MSCs to downregulate inflammatory signaling pathways was prospectively validated using model system parameters with respect to two different mechanisms: extracellular ATP stimulates lymphocytes to suppress proliferation and induce apoptosis and with co-stimulation, it stimulates monocytes to release pro-inflammatory IL-1β. MSCs were co-cultured with immune cells using transwell inserts and compared to immune cell only groups.ResultsHydrolysis of ATP was efficiently modeled by first-order enzyme kinetics. For in vitro culture, the rate at which a single cell can hydrolyize ATP is 8.9 nmol/min. In the presence of extracellular ATP, cocultures of MSCs reduced cytotoxicity and allows for proliferation of lymphocytes while limiting IL-1β secretion from monocytes.ConclusionsSuch use of these models may allow for better dosing predictions for MSCs to be used therapeutically for chronic inflammatory diseases such as rheumatoid arthritis, diabetes, pancreatitis, and other systemic inflammatory response syndromes. For the first time, the effect of MSCs on ATP hydrolysis in immune cell response is quantitatively analyzed on a cell-molecule basis by modeling the hydrolysis as an enzyme-substrate reaction. The results also give insight into MSCs' dynamic response mechanisms to ameliorate effects of extracellular ATP whether it be through positive or negative regulation.

Project description:BackgroundProgress has been made worldwide in reducing chronic undernutrition and rates of linear growth stunting in children under 5 y of age, although rates still remain high in many regions. Policies, programs, and interventions supporting maternal and child health and nutrition have the potential to improve child growth and development.ObjectiveThis article synthesizes the available global evidence on the drivers of national declines in stunting prevalence and compares the relative effect of major drivers of stunting decline between countries.MethodsWe conducted a systematic review of published peer-reviewed and gray literature analyzing the relation between changes in key determinants of child linear growth and contemporaneous changes in linear growth outcomes over time.ResultsAmong the basic determinants of stunting assessed within regression-decomposition analyses, improvement in asset index score was a consistent and strong driver of improved linear growth outcomes. Increased parental education was also a strong predictor of improved child growth. Of the underlying determinants of stunting, reduced rates of open defecation, improved sanitation infrastructure, and improved access to key maternal health services, including optimal antenatal care and delivery in a health facility or with a skilled birth attendant, all accounted for substantially improved child growth, although the magnitude of variation explained by each differed substantially between countries. At the immediate level, changes in several maternal characteristics predicted modest stunting reductions, including parity, interpregnancy interval, and maternal height.ConclusionsUnique sets of stunting determinants predicted stunting reduction within countries that have reduced stunting. Several common drivers emerge at the basic, underlying, and immediate levels, including improvements in maternal and paternal education, household socioeconomic status, sanitation conditions, maternal health services access, and family planning. Further data collection and in-depth mixed-methods research are required to strengthen recommendations for those countries where the stunting burden remains unacceptably high.

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A Brief Overview of Global Trends in MSC-Based Cell Therapy.

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A Brief Overview of Global Trends in MSC-Based Cell Therapy.

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