Differential Effects of Culture Senescence and Mechanical Stimulation on the Proliferation and Leiomyogenic Differentiation of MSC from Different Sources: Implications for Engineering Vascular Grafts

Abstract

We examined the effects of senescence on the proliferation and leiomyogenic differentiation potential of mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs) or hair follicles (HF-MSCs). To this end, we compared ovine HF-MSCs and BM-MSCs in terms of their proliferation and differentiation potential to the smooth muscle cell lineage. We discovered that HF-MSCs are less susceptible to culture senescence compared with BM-MSCs. We hypothesized that application of mechanical forces may enhance the contractility and mechanical properties of vascular constructs prepared from senescent MSCs. Interestingly, HF-MSCs and BM-MSCs responded differently to changes in the mechanical microenvironment, suggesting that despite phenotypic similarities, MSCs from different anatomic locations may activate different pathways in response to the same microenvironmental factors. In turn, this may also suggest that cell-based tissue regeneration approaches may need to be tailored to the stem cell origin, donor age, and culture time for optimal results.

A comprehensive study on donor‐matched comparisons of three types of mesenchymal stem cells‐containing cells from human dental tissue

“…MSCs enter senescence almost immediately from the moment in vitro culture is initiated. 44,45 Although we also emphasize that serial subcultivation impaired the performance of these cells, the threshold causing even a single passage in vitro to age cells to a degree to which their clinical use is compromised has not yet been addressed.…”

Arterial grafts exhibiting unprecedented cellular infiltration and remodeling in vivo: The role of cells in the vascular wall

“…Nevertheless, maturation of incoming host cells into contractile SMCs, suggests that donor medial cells may not be necessary for generation of functional SIS-Fibrin grafts. This is important as isolation and expansion of SMCs to the numbers required for engineering arteries of clinically relevant length is time consuming and cell quality declines significantly with donor age and culture senescence [33–36]. Since the majority of patients in need of vascular grafts are elderly, bypassing the requirement for donor SMCs in the vascular wall may decrease the time and cost of TEV fabrication, thereby increasing their potential for clinical use.…”

Adipose Tissue-Derived Stem Cells in Regenerative Medicine

“…Due to their wide availability MSCs represent an interesting cell source for regenerative medicine and are commonly isolated from the bone marrow [2,3]. However, bone marrow-derived MSCs are suboptimal for clinical use due to the required highly invasive aspiration procedure and the decline in both their proliferation and differentiation potential with increasing senescence [4]. In search for an alternative stem cell source at the beginning of the 21st century, Zuk et al [5] introduced a multipotent, undifferentiated, self-renewing progenitor cell population isolated from adipose tissue that is morphologically and phenotypically similar to the MSCs.…”