Human versus porcine mesenchymal stromal cells: phenotype, differentiation potential, immunomodulation and cardiac improvement after transplantation

Abstract

Although mesenchymal stromal cells (MSCs) have been applied clinically to treat cardiac diseases, it is unclear how and to which extent transplanted MSCs exert their beneficial effects. To address these questions, pre-clinical MSC administrations are needed for which pigs appear to be the species of choice. This requires the use of porcine cells to prevent immune rejection. However, it is currently unknown to what extent porcine MSCs (pMSCs) resemble human MSCs (hMSCs). Aim of this study was to compare MSC from porcine bone marrow (BM) with human cells for phenotype, multi-lineage differentiation potential, immune-modulatory capacity and the effect on cardiac function after transplantation in a mouse model of myocardial infarction. Flow cytometric analysis revealed that pMSC expressed surface antigens also found on hMSC, including CD90, MSCA-1 (TNAP/W8B2 antigen), CD44, CD29 and SLA class I. Clonogenic outgrowth was significantly enriched following selection of CD271+ cells from BM of human and pig (129 ± 29 and 1961 ± 485 fold, respectively). hMSC and pMSC differentiated comparably into the adipogenic, osteogenic or chondrogenic lineages, although pMSC formed fat much faster than hMSC. Immuno-modulation, an important feature of hMSC, was clearly demonstrated for pMSC when co-cultured with porcine peripheral blood cells stimulated with PMA and pIL-2. Finally, pMSC transplantation after myocardial infarction attenuated adverse remodelling to a similar extent as hMSC when compared to control saline injection. These findings demonstrate that pMSCs have comparable characteristics and functionality with hMSCs, making reliable extrapolation of pre-clinical pMSC studies into a clinical setting very well possible.

Telocytes of the mammary gland stroma

“…In this regard, the CD34-positive but CD117/c-kit negative phenotype we found in this study can indicate rejection of an endothelial tip cell diagnosis, HSCs being already rejected when the stromal compartment is observed. This reinforces a mesenchymal stem/progenitor phenotype of the stromal mammary fibroblastoid cells we studied, which is supported by recent experiments in which TCs were found positive for CD29 [3], a known MSCs marker [26,46].…”

Comparative immunophenotyping of equine multipotent mesenchymal stromal cells: An approach toward a standardized definition

“…MSCs isolated from different tissues of pigs robustly express CD 90 (54,(62)(63)(64) and CD 105 (54). CD 73 investigation in pig is hampered by a lack of cross-reactive mAbs (63).…”

Amniotic Fluid-Derived Stem Cells for Cardiovascular Tissue Engineering Applications

“…This work is motivated by similar studies performed using MSC, which have been shown to improve cardiac function when injected into the heart post-MI. [59][60][61][62] A summary of AFSC implantation studies and results can be found in Table 4.…”