Effects of Donor Age, Gender, and In Vitro Cellular Aging on the Phenotypic, Functional, and Molecular Characteristics of Mouse Bone Marrow-Derived Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) are a very important adult stem cell population with a multitude of potential applications in regenerative medicine. The thorough characterization of the bone marrow MSC (BM-MSC) population derived from the BALB/c species was essential, considering the significance of the murine model amongst animal models. In the present study, we examined the effect of gender, age, and in vitro culture on the basic properties (proliferation, differentiation, and immunosuppressive potential) of BM-MSCs. We found a decline in the progenitor frequencies from the BM of adult mice, lower MSC frequencies in all female donors, and an increase in the BM-MSC proliferation rate upon in vitro propagation. We also examined BM-MSCs for the expression of the 3 major embryonic stem cell transcription factors, Oct3/4, Sox-2, and Nanog, as well as 2 mRNA binding proteins, coding region determinant binding protein/insulin-like growth factor 2 mRNA binding protein 1 (Crd-bp/Imp1) and Deleted in azoospermia-like (Dazl), which are expressed in primitive stem cells, umbilical cord blood-hematopoietic stem cells and amniotic fluid stem cells, respectively. Further, it has been reported that these 2 genes are critical for embryonic development. In this study, therefore, we report, for the first time, the expression of Crd-bp/Imp1 and Dazl in BM-MSCs. Dazl, Oct3/4, and Sox2 were detected in relatively low levels in contrast to Crd-bp/Imp1, its major target c-Myc, as well as Nanog, which were expressed redundantly, irrespective of sex, donor age, or in vitro passaging. These findings could further support the extrinsic theory of aging of the MSC population and the potential implication of embryonic genes in adult stem cell physiology.

Adipose-Derived Mesenchymal Stromal Cells From Aged Patients With Coronary Artery Disease Keep Mesenchymal Stromal Cell Properties but Exhibit Characteristics of Aging and Have Impaired Angiogenic Potential

“…Most of the data regarding ADSC regenerative potential were obtained from cells delivered from relatively healthy young donors; however, it was known that aging and disease itself may negatively affect MSC activities [21][22][23][24][25][26], including proliferation and differentiation potential [27][28][29][30] as well as angiogenic properties [29,31]. Because MSCs are considered to be components of the vessel wall and take part in its reparation after injury, their cellular modification due to aging can be an important pathogenic factor of agerelated diseases such as atherosclerosis, diabetes, and arterial hypertension [32].…”

miR-543 and miR-590-3p regulate human mesenchymal stem cell aging via direct targeting of AIMP3/p18

“…Stem cell depletion or loss-of-function was proposed as a process that causes organismal aging (Janzen et al 2006;Katsara et al 2011). To investigate whether AIMP3/p18 is involved in the in vivo aging process as well as in vitro aging in MSCs, we isolated and cultured mouse bone marrow-derived mesenchymal stem cells (mBM-MSCs) from 4-week-old (young) and 19-monthold (aged) C57BL/6 mice.…”

Potently Immunosuppressive 5-Fluorouracil–Resistant Mesenchymal Stromal Cells Completely Remit an Experimental Autoimmune Disease

“…RT-PCR analysis for Oct-3/4 and Nanog Total MSC mRNA was isolated, and first-strand cDNA was amplified for Oct-3/4 and Nanog, as described (16). mRNA from murine embryonic stem cells used as positive control was a gift from Dr. Paul Verma (Monash Institute of Medical Research, Monash University, Australia).…”