Mesenchymal stromal cell infusions for acute graft-versus-host disease: Rationale, data, and unanswered questions

Seng, Amara; Dunavin, Neil

doi:10.1002/acg2.14

Cited by 3 publications

(3 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since then, several clinical and preclinical studies have been performed with controversial results due to the heterogeneity in the treatment schedules (ie, MSC concentration, dose number, administration route, and timing) and to other factors, such as MSC tissue origin and inflammatory status of the recipient . Similar controversial results and side effects (eg, pulmonary embolization) were shown by preclinical studies performed in mouse models …”

Section: Introductionmentioning

confidence: 97%

“…[17][18][19][20][21] Similar controversial results and side effects (eg, pulmonary embolization) were shown by preclinical studies performed in mouse models. [22][23][24] Human bone marrow-derived MSCs (hBM-MSCs) are a heterogeneous fibroblast-like cell population, including both multipotent stem cells with the ability to form bone, cartilage, and adipose tissue in vitro 25 and stromal cell components that regulate hematopoietic stem cell niche through specific cell-to-cell interactions and soluble factor release. 26 In 2006, the International Society for Cell & Gene Therapy (ISCT) established the minimal criteria to define MSCs, that is, the ability to grow as adherent cells, the membrane surface expression of a marker combination pattern, including CD73, CD90, and CD105 together with the lack of CD14, CD31, CD34, CD45, and HLA-DR expression, and the ability to differentiate into adipocytes, osteoblasts, and chondrocytes.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Functional dosing of mesenchymal stromal cell-derived extracellular vesicles for the prevention of acute graft-versus-host-disease

et al. 2020

View full text Add to dashboard Cite

Graft‐vs‐host‐disease (GvHD) is currently the main complication of allogeneic hematopoietic stem cell transplantation. Mortality and morbidity rates are particularly high, especially in steroid‐refractory acute GvHD (aGvHD). Immune regulatory human bone marrow mesenchymal stromal cells (hMB‐MSCs) represent a therapeutic approach to address this issue. Unfortunately, their effect is hardly predictable in vivo due to several variables, that is, MSC tissue origin, concentration, dose number, administration route and timing, and inflammatory status of the recipient. Interestingly, human bone marrow MSC‐derived extracellular vesicles (hBM‐MSC‐EVs) display many of the hBM‐MSC immunoregulatory properties due to their content in paracrine factors that greatly varies according to the collection method. In this study, we focused on the immunological characterization of hBM‐MSC‐EVs on their capability of inducing regulatory T‐cells (T‐regs) both in vitro and in a xenograft mouse model of aGvHD. We correlated these data with the aGvHD incidence and degree following hBM‐MSC‐EV intravenous administration. Thus, we first quantified the EV immunomodulation in vitro in terms of EV immunomodulatory functional unit (EV‐IFU), that is, the lowest concentration of EVs leading in vitro to at least threefold increase of the T‐regs compared with controls. Second, we established the EV therapeutic dose in vivo (EV‐TD) corresponding to 10‐fold the in vitro EV‐IFU. According to this approach, we observed a significant improvement of both mouse survival and control of aGvHD onset and progression. This study confirms that EVs may represent an alternative to whole MSCs for aGvHD prevention, once the effective dose is reproducibly identified according to EV‐IFU and EV‐TD definition.

show abstract

Section: Introductionmentioning

confidence: 97%

mentioning

confidence: 99%

Functional dosing of mesenchymal stromal cell-derived extracellular vesicles for the prevention of acute graft-versus-host-disease

et al. 2020

View full text Add to dashboard Cite

show abstract

“…More studies are needed to obtain correlative research data [94,95]. This outcome results in the first Food and Drug Administration (FDA) approved MSCs product in the United States [96,97].…”

Section: Msc Use In Clinical Studies 61 Clinical Potential and Markementioning

confidence: 99%

Alternative Immune-Mediated-Based Methods in the Aplastic Anemia Treatment

Gonzaga¹,

Policiquio²,

Wenceslau³

et al. 2021

Human Blood Group Systems and Haemoglobinopathies

View full text Add to dashboard Cite

Acquired aplastic anemia (AA) is characterized by partial or total bone marrow (BM) destruction resulting in pancytopenia. Most of the acquired AA is the result of autoimmune condition the imbalance between T-regulatory cells (Treg), abnormal cytokines production and cytotoxic T cells activation, leading to the hematopoietic stem cells (HSCs) death. The first-line treatment is given by HSC transplant, but some patients did not respond to the treatment. Therefore, new technologies need to treat AA nonresponder patients. Studies are in progress to test the efficacy of stem cell-based therapeutic as mesenchymal stem cells (MSCs), which confer low immunogenicity and are reliable allogeneic transplants in refractory severe AA cases. Furthermore, MSCs comprise the BM stromal niche and have an important role in supporting hematopoiesis by secreting regulatory cytokines, providing stimulus to natural BM microenvironment. In addition, MSCs have immunomodulatory property and are candidates for efficient supporting AA therapy.

show abstract

Genetically engineered mesenchymal stromal cells as a new trend for treatment of severe acute graft-versus-host disease

Shahbaz

Mansourabadi

Jafari

2022

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Mesenchymal Stem cells (MSCs) are a population of non-hematopoietic and self-renewing cells characterized by the potential to differentiate into different cell subtypes. MSCs have interesting features which have attracted a lot of attention in various clinical investigations. Some basic features of MSCs are including the weak immunogenicity (absence of MHC-II and costimulatory ligands accompanied by the low expression of MHC-I) and the potential of plasticity and multi-organ homing via expressing related surface molecules. MSCs by immunomodulatory effects could also ameliorate several immune-pathological conditions like graft-versus-host diseases (GVHD). The efficacy and potency of MSCs are the main objections of MSCs therapeutic applications. It suggested that improving the MSC immunosuppressive characteristic via genetic engineering to produce therapeutic molecules consider as one of the best options for this purpose. In this review, we explain the functions, immunologic properties and clinical applications of MSCs to discuss the beneficial application of genetically modified MSCs in GVHD.

show abstract

Mesenchymal stromal cell infusions for acute graft-versus-host disease: Rationale, data, and unanswered questions

Cited by 3 publications

References 118 publications

Functional dosing of mesenchymal stromal cell-derived extracellular vesicles for the prevention of acute graft-versus-host-disease

Functional dosing of mesenchymal stromal cell-derived extracellular vesicles for the prevention of acute graft-versus-host-disease

Alternative Immune-Mediated-Based Methods in the Aplastic Anemia Treatment

Genetically engineered mesenchymal stromal cells as a new trend for treatment of severe acute graft-versus-host disease

Contact Info

Product

Resources

About