A Comparative Analysis of Multipotent Mesenchymal Stromal Cells derived from Different Sources, with a Focus on Neuroregenerative Potential

Abstract

Multipotent mesenchymal stromal cells (MScs) can be considered an accessible therapeutic tool for regenerative medicine. Here, we compared the growth kinetics, immunophenotypic and immunomodulatory properties, gene expression and secretome profile of MSCs derived from human adult bone marrow (BM-MSCs), adipose tissue (AT-MSCs) and Wharton's jelly (WJ-MSCs) cultured in clinically-relevant conditions, with the focus on the neuroregenerative potential. All the cell types were positive for CD10/CD29/CD44/CD73/CD90/CD105/HLA-ABC and negative for CD14/CD45/CD235a/ CD271/HLA-DR/VEGFR2 markers, but they differed in the expression of CD34/CD133/CD146/SSEA-4/ MSCA-1/CD271/HLA-DR markers. BM-MSCs displayed the highest immunomodulatory activity compared to AT-and WJ-MSCs. On the other hand, BM-MSCs secreted the lower content and had the lower gene expression of neurotrophic growth factors compared to other cell lines, which may be caused by the higher sensitivity of BM-MSCs to nutrient limitations. Despite the differences in growth factor secretion, the MSC secretome derived from all cell sources had a pronounced neurotrophic potential to stimulate the neurite outgrowth of DRG-neurons and reduce the cell death of neural stem/progenitor cells after H 2 o 2 treatment. Overall, our study provides important information for the transfer of basic MSC research towards clinical-grade manufacturing and therapeutic applications.

Bone Marrow-Derived Mononuclear Cell Transplants Decrease Retinal Gliosis in Two Animal Models of Inherited Photoreceptor Degeneration

“…Since these studies did not perform immunosuppression [ 65 , 68 ], we wonder whether the limited survival and the lack of integration of the transplanted cells could have been due to cell rejection [ 43 ]. Nonetheless, for the neuroprotective effects of hBM-MSCs, transplantation may depend more on their paracrine and immunomodulatory properties [ 37 , 54 , 60 ] than in their integration within the retina.…”

“…Stem cells (SC) can theoretically perform both these actions [ 33 , 34 ]. These cells can divide and differentiate into different cell types and, if transplanted to the retina, may substitute the damaged or lost retinal cells [ 35 , 36 ] and also secrete different factors that may prevent neuronal death [ 37 ]. SC can be obtained from different accessible tissues such as bone marrow, blood and adipose tissue [ 10 , 37 , 38 , 39 ].…”

“…These cells can divide and differentiate into different cell types and, if transplanted to the retina, may substitute the damaged or lost retinal cells [ 35 , 36 ] and also secrete different factors that may prevent neuronal death [ 37 ]. SC can be obtained from different accessible tissues such as bone marrow, blood and adipose tissue [ 10 , 37 , 38 , 39 ]. Two types of cells, mesenchymal stem cells or mononuclear/CD34+ stem cells, can be harvested from the bone marrow aspirate and have shown promising results in different animal models of neuronal degeneration [ 40 , 41 , 42 , 43 , 44 ], including photoreceptor degeneration [ 39 , 43 , 45 , 46 , 47 , 48 ].…”

“…The hBM-MSCs have been used in clinical trials to induce angiogenesis in myocardial, peripheral or other types of ischemia [ 49 , 50 ]. Although these cells have not been documented to differentiate in other cell types, they release different factors and show beneficial immunomodulatory and regenerative properties [ 37 , 50 ]. Thus, hBM-MSCs have been used with apparent vascular regenerative capabilities in animal models of retinal ischemia [ 44 , 51 , 52 ].…”

CD73 positive adipose derived mesenchymal stem cells enhance cardiac repair with experimental myocardial infarction by promoting angiogenesis

“…MSCs exhibit a variety of immunophenotypes. CD44, CD73, CD29, CD90 and CD105 are the most common markers of MSCs, which also lack cell surface antigen CD45 [13]. As reported by Florian et al, the expression patterns of CD73, CD105, CD90 varied in different morphological subsets [8].…”