Effects of continuous passage on immunomodulatory properties of human adipose-derived stem cells

Abstract

Human adipose-derived stem cells (hADSCs) have the ability to influence immune response, and hence are key cell sources for tissue repair and regeneration. In this study we explored the effect of continuous passage on the immunomodulatory properties of hADSCs to provide some advises for large-scale production of hADSCs for clinical applications. We found that after continuous passage, the specific surface markers expression levels as well as the adipogenic and osteogenic differentiation capacities of hADSCs had no obvious changes. However, the secretion levels of IL-10 and HGF reduced dramatically along with passage numbers. Furthermore, the INF-γ level was found higher in which medium peripheral blood mononuclear cells were co-cultured with hADSCs with higher passage numbers. Also, the in vivo experiments showed that the peritonitis model mice, which were injected with higher passage numbers of hADSCs, tended to have higher levels of inflammation. All these together indicated that continuous passage has only minor effect on the cell phenotypes but will impair the immunomodulatory properties of hADSCs. This suggests that hADSCs could be prepared by continuous passage, but only those cells of lower passage numbers would be ideal therapeutic tools.

Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases

“…ADMSCs derived from adults and elderly people were significantly less efficient at suppressing T cell proliferation and showed increased production of IFN-γ and decreased production of IL-10 compared with infant-derived ADSCs, indicating that an age-associated decline in the immunomodulatory capacity of ADMSCs occurs [52]. Sequential passage in vitro exerts a negative impact on the multipotency of ADMSCs [53], and long-term culture results in replicative senescence, genetic instability, and upregulated immune responses in ADMSCs and consequently reduces their therapeutic efficacy [54, 55]. Thus, ADMSCs isolated from infants or early-passage cells may have greater potential to be effective in promoting liver regeneration than ADMSCs obtained from adults and elderly people and late-passage ADMSCs.…”

Concise Review: Using Fat to Fight Disease: A Systematic Review of Nonhomologous Adipose-Derived Stromal/Stem Cell Therapies

“…If SVF cells are not immediately re‐administered to the patient, there must be processes for expansion, storage, and release of cells for clinical use . ASC that have been isolated and expanded for multiple passages may begin to undergo replicative senescence, which could lead to genetic instability, increased potential for immune response, and reduced efficacy as a cellular therapy . Additional studies should aim to compare SVF and ASC, as avoiding the need for culture and passage may reduce these risks.…”

MicroRNA-26a-modified adipose-derived stem cells incorporated with a porous hydroxyapatite scaffold improve the repair of bone defects

“…However, bone regeneration often requires a large number of MSCs and despite MSCs being universally expressed in numerous tissues, in the majority of cases they are difficult to isolate. Although in vitro expansion can increase the cell number, long term proliferation and continuous passage have adverse effects on the normal function of BMSCs ( 19 ). By contrast, ASCs are derived from adipose tissue and can be easily obtained in a large number.…”