Mesenchymal Stromal Cells: What Is the Mechanism in Acute Graft-Versus-Host Disease?

Dunavin, Neil; Dias, Ajoy; Li, Meizhang; McGuirk, Joseph P.

doi:10.3390/biomedicines5030039

Cited by 41 publications

(30 citation statements)

References 117 publications

(130 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The osteogenic differentiation potential of MSCs makes them successful in treating and managing bone fractures [97]. The ability of MSCs to modulate immune responses is considered as a safe and feasible strategy to treat Crohn's disease [98], systemic lupus erythematosus (SLE) [99,100], rheumatoid arthritis (RA) [101], GvHD [102], Type I diabetes [103] and so on. MSCs also prevent allergic airway inflammation and reduce the symptoms of severe asthma [104][105][106][107][108].…”

Section: Therapeutic Properties Of Mscsmentioning

confidence: 99%

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Fan

Zhang

et al. 2020

Cell. Mol. Life Sci.

369

282

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell-cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies. Keywords Regenerative potential • Integration of MSCs • Immunomodulation • Soluble factors • Cell-cell contact • Mitochondrial transfer • Extracellular vesicles Abbreviations AHR Airway hyper-responsiveness Alix ALG-2-interacting protein X Ang-1 Angiopoietin-1 ASCs Adipose-derived stem cells BAX BCL-2-associated X protein BCL-2 B-cell lymphoma 2 CASP3 Caspase 3 CX43 Connexin 43 CXCR4 Chemokine receptor type 4 DC Dendritic cell Cellular and Molecular Life Sciences

show abstract

Section: Therapeutic Properties Of Mscsmentioning

confidence: 99%

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Fan

Zhang

et al. 2020

Cell. Mol. Life Sci.

369

282

View full text Add to dashboard Cite

show abstract

“…Evidence from in vitro studies and animal models indicates that bone marrow-derived MSCs have immunosuppressive and immunomodulatory functions [13][14][15][16][17][18][19]. Allogeneic tolerance, inhibition at immune checkpoints, and paracrine signaling are MSC mechanisms particularly relevant to aGVHD [20,21]. Results from initial clinical studies of MSCs have indicated favorable clinical response rates with an acceptable safety profile when used to treat steroid-refractory GVHD (SR-aGVHD) [22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

A Phase 3, Single-Arm, Prospective Study of Remestemcel-L, Ex Vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells for the Treatment of Pediatric Patients Who Failed to Respond to Steroid Treatment for Acute Graft-versus-Host Disease

Kurtzberg

Abdel‐Azim

Carpenter

et al. 2020

Biology of Blood and Marrow Transplantation

104

View full text Add to dashboard Cite

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) following hematopoietic cell transplantation (HSCT) is associated with poor clinical outcomes. Currently, there are no safe and effective therapies approved for use in the pediatric population under the age of 12 years. Accordingly, there is an urgent need for new treatments that are safe, well tolerated, and effective in managing this debilitating and potentially fatal complication of HSCT. In early phase clinical trials, mesenchymal stromal cells (MSCs) have demonstrated efficacy in the treatment of acute GVHD (aGVHD) in pediatric patients. We now report the results of a phase 3, prospective, single-arm, multicenter study (NCT02336230) in 54 children with primary SR-aGVHD who were naive to other immunosuppressant therapies for aGVHD treated with MSC product (remestemcel-L) dosed at 2 £ 10 6 cells/kg twice weekly for 4 weeks. Remestemcel-L therapy significantly improved day 28 overall response rate (OR) compared with the prespecified control OR value of 45% (70.4% versus 45%, P = .0003). The statistically significant OR (70.4%) was sustained through day 100, including an increase in complete response from 29.6% at day 28 to 44.4% at day 100. Overall survival was 74.1% at day 100 and 68.5% at day 180. Overall response in all participants at day 28 was highly predictive of improved survival through 180 days, and survival was significantly greater in day 28 responders compared with nonresponders through day 100 (86.8% versus 47.1% for responders and nonresponders, respectively, P = .0001) and through day 180 (78.9% versus 43.8%, P = .003). Remestemcel-L was well tolerated with no identified infusion-related toxicities or other safety concerns. This study provides robust, prospective evidence of the safety, tolerability, and efficacy of remestemcel-L as first-line therapy after initial steroid failure in pediatric SR-aGVHD.

show abstract

“…Mesenchymal stem cells (MSCs), acting as a pleiotropic immune regulator, are reported to suppress immune processes, in which nearly all immune cells including T cells, natural killer (NK) cells, B cells, and dendritic cells (DCs) are affected [4,[6][7][8][9]. In the recent years, more attention has paid to potential efficiency of MSCs in aGvHD as they show low toxicity and high expansion in vitro [5,10]. The immunomodulatory effects of MSCs are not always immunosuppressive as it is depending on inflammatory microenvironments [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

MiR-223 Derived from Mesenchymal Stem Cell Exosomes Alleviates Acute Graft-Versus-Host Disease

Liu¹,

Zhou²,

Wang³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Mesenchymal stem cells (MSCs) have been utilized in treating acute graft-versus-host disease (aGvHD) as they show strong immunosuppressive capacity, but the mechanisms are not well defined.Methods In this study, we demonstrated that microRNA-223 (miR-223) derived from exosomes secreted by human umbilical cord mesenchymal stem cells (huc-MSCs) and murine compact bone mesenchymal stem cells (mb-MSCs) could inhibit aGvHD progression by reducing the migration and homing of donor T cells in aGvHD mice.Results MiR-223 was one of the conserved microRNAs highly expressed in huc-MSCs exosomes and mMSCs exosomes, which was identified by high-throughput sequencing. MiR-223 derived from MSC exosomes showed enhanced immunosuppressive capacity, as it could inhibit expression of the target gene ICAM-1 and restrain adhesion and migration of T cells in vitro. Moreover, miR-223Agomir was effective in reducing the inflammatory reaction, and declining the donor T cells infiltration into the spleen, liver and intestine in aGvHD mice. Subsequently, it could alleviate aGvHD symptoms. Taken together, the MSC exosome derived miR-223 could attenuate aGvHD in mice through regulating ICAM-1 expression.Conclusions Our results unveil a new role for MSC exosomes derived miR-223 in the treatment of aGvHD.

show abstract

Mesenchymal Stromal Cells: What Is the Mechanism in Acute Graft-Versus-Host Disease?

Cited by 41 publications

References 117 publications

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

A Phase 3, Single-Arm, Prospective Study of Remestemcel-L, Ex Vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells for the Treatment of Pediatric Patients Who Failed to Respond to Steroid Treatment for Acute Graft-versus-Host Disease

MiR-223 Derived from Mesenchymal Stem Cell Exosomes Alleviates Acute Graft-Versus-Host Disease

Contact Info

Product

Resources

About