Transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than Wharton's jelly mesenchymal stromal cells.

BACKGROUND: Mesenchymal stromal cells (MSCs) from various tissues have shown moderate therapeutic efficacy in reversing liver fibrosis in preclinical models. Here, we compared the relative therapeutic potential of pooled, adult human bone marrow (BM)- and neonatal Wharton's jelly (WJ)-derived MSCs to treat CCl4-induced liver fibrosis in rats. METHODS: Sprague-Dawley rats were injected with CCl4 for 8 weeks to induce irreversible liver fibrosis. Ex-vivo expanded, pooled human MSCs obtained from BM and WJ were intravenously administered into rats with liver fibrosis at a dose of 10 × 106 cells/animal. Sham control and vehicle-treated animals served as negative and disease controls, respectively. The animals were sacrificed at 30 and 70 days after cell transplantation and hepatic-hydroxyproline content, histopathological, and immunohistochemical analyses were performed. RESULTS: BM-MSCs treatment showed a marked reduction in liver fibrosis as determined by Masson's trichrome and Sirius red staining as compared to those treated with the vehicle. Furthermore, hepatic-hydroxyproline content and percentage collagen proportionate area were found to be significantly lower in the BM-MSCs-treated group. In contrast, WJ-MSCs treatment showed less reduction of fibrosis at both time points. Immunohistochemical analysis of BM-MSCs-treated liver samples showed a reduction in α-SMA+ myofibroblasts and increased number of EpCAM+ hepatic progenitor cells, along with Ki-67+ and human matrix metalloprotease-1+ (MMP-1+) cells as compared to WJ-MSCs-treated rat livers. CONCLUSIONS: Our findings suggest that BM-MSCs are more effective than WJ-MSCs in treating liver fibrosis in a CCl4-induced model in rats. The superior therapeutic activity of BM-MSCs may be attributed to their expression of certain MMPs and angiogenic factors.

Impact of passing mesenchymal stem cells through smaller bore size needles for subsequent use in patients for clinical or cosmetic indications.

BACKGROUND: Numerous preclinical and clinical studies have investigated the regenerative potential and the trophic support of mesenchymal stem cells (MSCs) following their injection into a target organ. Clinicians favor the use of smallest bore needles possible for delivering MSCs into vascular organs like heart, liver and spleen. There has been a concern that small needle bore sizes may be detrimental to the health of these cells and reduce the survival and plasticity of MSCs. METHODS: In this report, we aimed to investigate the smallest possible bore size needle which would support the safe delivery of MSCs into various tissues for different clinical or cosmetic applications. To accomplish this we injected cells via needle sizes 24, 25 and 26 G attached to 1 ml syringe in the laboratory and collected the cells aseptically. Control cells were ejected via 1 ml syringe without any needle. Thereafter, the needle ejected cells were cultured and characterized for their morphology, attachment, viability, phenotypic expression, differentiation potential, cryopreservation and in vivo migration abilities. In the second phase of the study, cells were injected via 26 G needle attached to 1 ml syringe for 10 times. RESULTS: Similar phenotypic and functional characteristics were observed between ejected and control group of cells. MSCs maintained their cellular and functional properties after single and multiple injections. CONCLUSIONS: This study proves that 26 G bore size needles can be safely used to inject MSCs for clinical/therapeutics purposes.