A Comparison of Phenotypic and Functional Properties of Mesenchymal Stromal Cells and Multipotent Adult Progenitor Cells

Khan, Reenam S.; Newsome, Philip N.

doi:10.3389/fimmu.2019.01952

Cited by 42 publications

(48 citation statements)

References 197 publications

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“…In the newly registered advanced COVID-19 trials of Athersys (MAPC-/BM-MSC-based MultiStem R product) and Mesoblasts (BM-MSC-based), the cell product is delivered IV. These cell products have low TF/CD142 expression (6)(7)(8)74), which may be tolerated with appropriate adjunct infusion protocols and welldefined patient inclusion/exclusion criteria (e.g., excluding prehistory of patient coagulopathy). Both Athersys and Mesoblast reported preliminary safety and efficacy in preceding studies and have now advanced to phase II/III studies with prior approval by the corresponding regulatory authorities such as the FDA (29).…”

Section: Weighing Risk and Benefit Of Intravenous Vs Intramuscular Cmentioning

confidence: 99%

MSC Therapies for COVID-19: Importance of Patient Coagulopathy, Thromboprophylaxis, Cell Product Quality and Mode of Delivery for Treatment Safety and Efficacy

et al. 2020

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Numerous clinical trials of mesenchymal stromal/stem cells (MSCs) as a new treatment for coronavirus-induced disease (COVID-19) have been registered recently, most of them based on intravenous (IV) infusion. There is no approved effective therapy for COVID-19, but MSC therapies have shown first promise in the treatment of acute respiratory distress syndrome (ARDS) pneumonia, inflammation, and sepsis, which are among the leading causes of mortality in COVID-19 patients. Many of the critically ill COVID-19 patients are in a hypercoagulable procoagulant state and at high risk for disseminated intravascular coagulation, thromboembolism, and thrombotic multiorgan failure, another cause of high fatality. It is not yet clear whether IV infusion is a safe and effective route of MSC delivery in COVID-19, since MSC-based products express variable levels of highly procoagulant tissue factor (TF/CD142), compromising the cells' hemocompatibility and safety profile. Of concern, IV infusions of poorly characterized MSC products with unchecked (high) TF/CD142 expression could trigger blood clotting in COVID-19 and other vulnerable patient populations and further promote the risk for thromboembolism. In contrast, well-characterized products with robust manufacturing procedures and optimized modes of clinical delivery hold great promise for ameliorating COVID-19 by exerting their beneficial immunomodulatory effects, inducing tissue repair and organ protection. While the need for MSC therapy in COVID-19 is apparent, integrating both innate and adaptive immune compatibility testing into the current guidelines for cell, tissue, and organ transplantation is critical for safe and effective therapies. It is paramount to only use wellcharacterized, safe MSCs even in the most urgent and experimental treatments. We here propose three steps to mitigate the risk for these vulnerable patients: (1) updated Moll et al. MSC Therapies for COVID-19 clinical guidelines for cell and tissue transplantation, (2) updated minimal criteria for characterization of cellular therapeutics, and (3) updated cell therapy routines reflecting specific patient needs.

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Section: Weighing Risk and Benefit Of Intravenous Vs Intramuscular Cmentioning

confidence: 99%

MSC Therapies for COVID-19: Importance of Patient Coagulopathy, Thromboprophylaxis, Cell Product Quality and Mode of Delivery for Treatment Safety and Efficacy

et al. 2020

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“…MultiStem ® bone marrow-derived multipotent adult progenitor cells (MAPC) have been investigated in the Phase 1/2 MUST-ARDS clinical trial, an open-label dose-escalation study followed by randomized placebo-controlled trial (NCT02611609). MAPC meets the minimal defining criteria for MSCs but are reported to have a greater proliferation capacity than traditional MSCs [22,127]. Preliminary results report MultiStem ® treatment reduced 28-day mortality (from 40% to 25%), increased ventilator-free days (from 9.2 to 12.9 days), and increased ICU-free days (from 9.2 to 10.3 days).…”

Section: Mscs In Ards and Sepsis Clinical Trials (Summary Table 2 Andmentioning

confidence: 99%

Mesenchymal stromal cells for acute respiratory distress syndrome (ARDS), sepsis, and COVID-19 infection: optimizing the therapeutic potential

Gorman

Millar

O’Kane

2020

Expert Review of Respiratory Medicine

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Introduction: Mesenchymal stromal (stem) cell (MSC) therapies are emerging as a promising therapeutic intervention in patients with Acute Respiratory Distress Syndrome (ARDS) and sepsis due to their reparative, immunomodulatory, and antimicrobial properties. Areas covered: This review provides an overview of Mesenchymal stromal cells (MSCs) and their mechanisms of effect in ARDS and sepsis. The preclinical and clinical evidence to support MSC therapy in ARDS and sepsis is discussed. The potential for MSC therapy in COVID-19 ARDS is discussed with insights from respiratory viral models and early clinical reports of MSC therapy in COVID-19. Strategies to optimize the therapeutic potential of MSCs in ARDS and sepsis are considered including preconditioning, altered gene expression, and alternative cell-free MSC-derived products, such as extracellular vesicles and conditioned medium. Expert opinion: MSC products present considerable therapeutic promise for ARDS and sepsis. Preclinical investigations report significant benefits and early phase clinical studies have not highlighted safety concerns. Optimization of MSC function in preclinical models of ARDS and sepsis has enhanced their beneficial effects. MSC-derived products, as cell-free alternatives, may provide further advantages in this field. These strategies present opportunity for the clinical development of MSCs and MSC-derived products with enhanced therapeutic efficacy.

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“…Although, low or null immunogenicity for allogeneic MSCs has been claimed ( Le Blanc et al, 2003 ; Escacena et al, 2015 ), recent in vivo and in vitro evidence suggests that MSCs generate both innate and adaptive host immune responses ( Caplan et al, 2019 ). However, anti-MSC responses are lower than those against other allogeneic cells are ( Khan and Newsome, 2019 ), perhaps because MSCs do not express MHC class II antigens or co-stimulatory molecules. Therefore, the balance between their immunogenicity and the release of immunosuppressive factors, highly dependent on the local microenvironment, determines the MSC behavior ( Khan and Newsome, 2019 ).…”

Section: Allogeneic or Autologous Mesenchymal Stromal Cells For Theramentioning

confidence: 99%

“…However, anti-MSC responses are lower than those against other allogeneic cells are ( Khan and Newsome, 2019 ), perhaps because MSCs do not express MHC class II antigens or co-stimulatory molecules. Therefore, the balance between their immunogenicity and the release of immunosuppressive factors, highly dependent on the local microenvironment, determines the MSC behavior ( Khan and Newsome, 2019 ). Even more, this cytotoxic activity is important for MSC-mediated immunosuppression because it results in phagocytosis of apoptotic cells and then macrophage polarization ( Galleu et al, 2017 ; de Witte et al, 2018 ).…”

Section: Allogeneic or Autologous Mesenchymal Stromal Cells For Theramentioning

confidence: 99%

The Current Status of Mesenchymal Stromal Cells: Controversies, Unresolved Issues and Some Promising Solutions to Improve Their Therapeutic Efficacy

García‐Bernal

García-Arranz

Yáñez

et al. 2021

Front. Cell Dev. Biol.

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Mesenchymal stromal cells (MSCs) currently constitute the most frequently used cell type in advanced therapies with different purposes, most of which are related with inflammatory processes. Although the therapeutic efficacy of these cells has been clearly demonstrated in different disease animal models and in numerous human phase I/II clinical trials, only very few phase III trials using MSCs have demonstrated the expected potential therapeutic benefit. On the other hand, diverse controversial issues on the biology and clinical applications of MSCs, including their specific phenotype, the requirement of an inflammatory environment to induce immunosuppression, the relevance of the cell dose and their administration schedule, the cell delivery route (intravascular/systemic vs. local cell delivery), and the selected cell product (i.e., use of autologous vs. allogeneic MSCs, freshly cultured vs. frozen and thawed MSCs, MSCs vs. MSC-derived extracellular vesicles, etc.) persist. In the current review article, we have addressed these issues with special emphasis in the new approaches to improve the properties and functional capabilities of MSCs after distinct cell bioengineering strategies.

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A Comparison of Phenotypic and Functional Properties of Mesenchymal Stromal Cells and Multipotent Adult Progenitor Cells

Cited by 42 publications

References 197 publications

MSC Therapies for COVID-19: Importance of Patient Coagulopathy, Thromboprophylaxis, Cell Product Quality and Mode of Delivery for Treatment Safety and Efficacy

MSC Therapies for COVID-19: Importance of Patient Coagulopathy, Thromboprophylaxis, Cell Product Quality and Mode of Delivery for Treatment Safety and Efficacy

Mesenchymal stromal cells for acute respiratory distress syndrome (ARDS), sepsis, and COVID-19 infection: optimizing the therapeutic potential

The Current Status of Mesenchymal Stromal Cells: Controversies, Unresolved Issues and Some Promising Solutions to Improve Their Therapeutic Efficacy

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