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Updated: May 24, 2026
Isolation, Culture, and Differentiation of Bone Marrow Stromal Cells and Osteoclast Progenitors from Mice
Published on: January 6, 2018
Bone marrow derived mesenchymal stem cells from aged mice have reduced wound healing, angiogenesis, proliferation and
Mahmood Saba Choudhery1, Mohsin Khan, Ruhma Mahmood
1National Center of Excellence in Molecular Biology, 87 West Canal Bank Road, University of the Punjab, Lahore, Pakistan.
Abstract:
Decline in the function of stem cells with age, such as other cells of the body, results in an imbalance between loss and renewal. Increasing age of the donor thus diminishes the effectiveness of MSCs (mesenchymal stem cells) transplantation in age-related diseases. The clinical use of stem cell therapies needs autologous stem cell transplantation; it is essential therefore to study the repair ability and survivability of cells before transplantation. Bone marrow derived MSCs possess multi-lineage differentiation potential, but aging adversely affects their therapeutic efficacy. MSCs from young (2-3 months) and aged (23-24 months) GFP (green fluorescent protein)-expressing C57BL/6 mice were isolated and their regenerative potential was assessed in vitro. Real-time RT-PCR (reverse transcriptase-PCR) showed significantly higher expression of Sirt1 in MSCs isolated from young than older animals. Down-regulation of VEGF (vascular endothelial growth factor), SDF-1 (stromal-cell-derived factor 1), AKT (also known as protein kinase B) and up-regulation of p53, p21, Bax and p16 occurred in aged cells. Tube formation, wound healing and proliferative abilities of the young MSCs were better than the aged MSCs. The results suggest that age-related increased expression of apoptotic and senescent genes, with concomitant decrease in Sirt1 gene expression, inhibits to some extent stem cell functioning.
Insights
Aging impairs mesenchymal stem cell (MSC) function, reducing their therapeutic potential. Young MSCs show better regenerative capacity than aged MSCs due to distinct gene expression profiles.
Area of Science:
- Stem cell biology
- Gerontology
- Regenerative medicine
Background:
- Stem cell function declines with age, impacting tissue repair and renewal.
- Mesenchymal stem cells (MSCs) are crucial for regenerative therapies, but their efficacy diminishes in older donors.
- Autologous stem cell transplantation requires understanding cell repair and survival before clinical application.
Purpose of the Study:
- To investigate the impact of aging on the regenerative potential and gene expression of bone marrow-derived MSCs.
- To compare the in vitro functional characteristics of MSCs from young and aged mice.
- To identify molecular mechanisms underlying age-related changes in MSC function.
Main Methods:
- Isolation and in vitro assessment of MSCs from young (2-3 months) and aged (23-24 months) GFP-expressing C57BL/6 mice.
- Real-time RT-PCR to analyze gene expression, including Sirt1, VEGF, SDF-1, AKT, p53, p21, Bax, and p16.
- Evaluation of MSC functional assays: tube formation, wound healing, and proliferation.
Main Results:
- Aged MSCs exhibited significantly lower Sirt1 gene expression compared to young MSCs.
- Down-regulation of pro-angiogenic and survival genes (VEGF, SDF-1, AKT) and up-regulation of apoptotic/senescence genes (p53, p21, Bax, p16) were observed in aged MSCs.
- Young MSCs demonstrated superior tube formation, wound healing, and proliferative abilities over aged MSCs.
Conclusions:
- Aging adversely affects MSC function by altering the expression of key regulatory genes.
- Increased expression of apoptotic and senescent markers, coupled with decreased Sirt1 expression, contributes to impaired stem cell function in aged individuals.
- These findings highlight the challenges of using aged MSCs in regenerative medicine and underscore the need for strategies to enhance their therapeutic efficacy.
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