Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cells

Abstract

Background: Bone marrow-derived mesenchymal stem cells (BMSCs) are a widely researched adult stem cell population capable of differentiation into various lineages. Because many promising applications of tissue engineering require cell expansion following harvest and involve the treatment of diseases and conditions found in an aging population, the effect of donor age and ex vivo handling must be understood in order to develop clinical techniques and therapeutics based on these cells. Furthermore, there currently exists little understanding as to how these two factors may be influenced by one another.

Cartilage Matrix Formation by Bovine Mesenchymal Stem Cells in Three-dimensional Culture Is Age-dependent

“…Aged MSC pellets with TGF-b3 accumulated less GAG and collagen than immature MSCs. This decline in MSC potential has been observed in both murine [30] and male (but not female) human [41] MSCs in pellet format, although donors were skeletally mature. Another study suggests a small decline in matrix production from adult MSCs compared with fetal cells [5].…”

“…Rabbit tendon injuries repaired with autologous MSCs from young or aged animals produced repair tissue with equivalent material properties [16]. The literature is conflicting whether osteogenic and adipogenic MSC differentiation is agedependent, with some studies suggesting it is independent of age [42,46,49] and others dependent on age [14,30]. For human MSC chondrogenesis, both age-dependent and age-independent findings have also been noted [37,41,43].…”

Morphological, molecular and functional differences of adult bone marrow- and adipose-derived stem cells isolated from rats of different ages

“…Indeed, restoration of mitogenic and growth signalling may rejuve-nate cells, and instead of entering in a senescence cycle the cells respond to growth factor induced 'reprogramming' that leads them to maintained proliferation despite the high passage number [13]. The results of recent studies showed that MSC harvested from donor animals of different ages and cultured for different numbers of passages showed a decrease in their chondrogenic and osteogenic potential with increasing passage number, whereas their adipogenic potential decrease with donor age [39]. Conversely, others have shown that there were no age related differences in rat MSC differentiation or changes in proliferation, attachment and senes-cence [10,11,40,41].…”

iPSC-MSCs Combined with Low-Dose Rapamycin Induced Islet Allograft Tolerance Through Suppressing Th1 and Enhancing Regulatory T-Cell Differentiation

“…MSCs have previously demonstrated their capacity to facilitate regeneration and regulate immune responses in a range of animal models; however, major factors related to life span and tumorigenicity limit their widespread use in a clinical setting [28][29][30][31][32]. Recent reports have described MSC-like cells derived from iPSCs [33][34][35] with a greater proliferative capacity, lower immunogenicity, and greater immunoregulatory function compared with primary MSC cultures [33,43,45].…”

“…Successive passages slow the proliferation rate, and MSCs progressively lose their multipotency and lack immunosuppressive activity. In addition, aging and age-related disorders significantly impair the survival and differentiation potential of BM-MSCs, thus limiting their therapeutic efficacy [28][29][30][31][32]. Therefore, it is important to identify alternative sources of MSCs before they can be used as a mainstream treatment for organ transplantation.…”