A comparison of the reparative and angiogenic properties of mesenchymal stem cells derived from the bone marrow of BALB/c and C57/BL6 mice in a model of limb ischemia

Abstract

IntroductionBALB/c mice and C57/BL6 mice have different abilities to recover from ischemia. C57/BL6 mice display increased vessel collateralization and vascular endothelial growth factor expression with a consequent rapid recovery from ischemia compared with BALB/c mice. Mesenchymal stem cells (MSCs) are one of the main cell types that contribute to the recovery from ischemia because, among their biological activities, they produce several proangiogenic paracrine factors and differentiate into endothelial cells. The objective of this study was to evaluate whether the MSCs of these two mouse strains have different inductive capacities for recovering ischemic limbs.MethodsMSCs from these two strains were obtained from the bone marrow, purified and characterized before being used for in vivo experiments. Limb ischemia was surgically induced in BALB/c mice, and MSCs were injected on the fifth day. The evolution of limb necrosis was evaluated over the subsequent month. Muscle strength was assessed on the 30th day after the injection, and then the animals were sacrificed to determine the muscle mass and perform histological analyses to detect cellular infiltration, capillary and microvessel densities, fibrosis, necrosis and tissue regeneration.ResultsThe MSCs from both strains promoted high level of angiogenesis similarly, resulting in good recovery from ischemia. However, BALB/c MSCs promoted more muscle regeneration (57%) than C57/BL6 MSCs (44%), which was reflected in the increased muscle strength (0.79 N versus 0.45 N).ConclusionThe different genetic background of MSCs from BALB/c mice and C57/BL6 mice was not a relevant factor in promoting angiogenesis of limb ischemia, because both cells showed a similar angiogenic activity. These cells also showed a potential myogenic effect, but the stronger effect promoted by BALB/c MSCs indicates that the different genetic background of MSCs was more relevant in myogenesis than angiogesis.

Mircrining the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy

“…For example, the secretome of naïve undifferentiated BM-derived MSCs is richer in pro-angiogenic factors as compared to the secretome of their osteogenic and chondrogenic derivatives [22]. Similarly, the secretome of MSCs subjected to ischemia varied in VEGF expression between the cells isolated from C57/ BL6 and Balb/c mouse strains [23]. This difference was also evident from the angiogenic response observed when the cells from the two sources were engrafted in an experimental model of hind-limb ischemia.…”

Proangiogenic Features of Mesenchymal Stem Cells and Their Therapeutic Applications

“…Moreover, the angiogenic applications of MSCs are not only based on their ability to differentiate into ECs, but also on their differentiation ability toward SMCs phenotype. In response to TGF- β , MSCs have been revealed to transdifferentiate into SMCs by direct contact with vascular ECs, mechanical stress, and prostaglandin F 2 α (PGF 2 α ) [ 61 , 62 ]. The intramuscular injection of TGF- β 1-induced human adipose tissue-derived MSCs could improve neovascularization and blood perfusion significantly [ 63 ].…”

Fibroblasts as a practical alternative to mesenchymal stem cells

“…It is important to note that these initial clinical experiences with MSC were in patients with oncological indications and no overt acceleration of cancer progression was noted. This has been a concern given that MSC are known to be angiogenic [ 20 – 25 ], produce mitogenic/antiapoptotic factors [ 26 – 32 ], and exert an immune suppressive effect [ 33 – 40 ]. Besides feasibility, these studies were important because they established the technique for ex vivo expansion and re-administration.…”