Telomere length, telomerase activity and osteogenic differentiation are maintained in adipose-derived stromal cells from senile osteoporotic SAMP6 mice

Abstract

Adipose tissue provides for a rich and easily accessible source of multipotent stromal cells and thus offers the potential for autologous cell-based therapy for a number of degenerative diseases. Senile osteoporosis is characterized by a reduction in bone quality, which is associated with inadequacies in bone marrow stromal cell (BMSC) differentiation. In the present study, we have characterized adipose-derived stromal cells (ASCs) isolated from aged osteoporotic mice and evaluated their suitability as a source of osteogenic precursor cells. Significant reductions in both tibia bone quality and telomere length in liver tissue were observed in the senescence-accelerated mouse prone 6 strain (SAMP6), as compared to the control age-matched senescence-accelerated mouse resistant 1 strain (SAMR1), thus confirming osteoporosis and accelerated ageing traits in this model. ASCs isolated from inguinal fat expressed mesenchymal surface markers and were capable of differentiating along the osteoblast, adipocyte and chondrocyte lineages. Telomere length was not compromised in ASCs from SAMP6 mice but was actually found to be significantly increased as compared to control SAMR1 mice. Furthermore, ASCs from both strains were comparable in terms of telomerase activity, p21 mRNA expression, SA-β-gal activity and proliferative capacity. The overall osteogenic and adipogenic potential of ASCs was comparable between SAMP6 and SAMR1 strains, as determined by quantitative molecular, biochemical and histological analyses. In conclusion, adipose tissue may represent a promising autologous cell source for the development of novel bone regenerative therapeutic strategies in the treatment of age-related osteoporosis.

Human Serine Protease HTRA1 Positively Regulates Osteogenesis of Human Bone Marrow-derived Mesenchymal Stem Cells and Mineralization of Differentiating Bone-forming Cells Through the Modulation of Extracellular Matrix Protein

“…Mouse adipose-derived stromal cells (mASCs) were isolated from the inguinal fat pads of SAMR1 mice (n ¼ 4) and purity confirmed by fluorescence-activated cell sorting (Sca1, 98%; CD29, 100%; CD105, 42%; CD34, 5%; CD45, 0.5%) as previously reported [21]. Mouse embryonic stem cells (mESCs) (E14 129/ Ola) are a well-established cell line and were maintained as previously described [22,23].…”

“…Well-established differentiation protocols were used to induce and analyze either osteogenesis or adipogenesis in mASCs and E14 129/Ola cells [21] and hBMSCs [24]. For differentiation assays, a starting density of 5,000 and 10,000 cells per square centimeter was used for human and mouse cells, respectively.…”

Efeito in vitro da triiodotironina sob o potencial osteogênico reduzido de células-tronco mesenquimais do tecido adiposo de ratas ovariectomizadas e com osteoporose

“…Diante dessa hipótese, os resultados apresentados neste estudo não surpreendem. No entanto, existem relatos de que a diferenciação osteogênica de CTM-TA subcutâneo é mantida em camundongos SAMP 6 com osteoporose (50). É provável que a redução do potencial osteogênico das CTM-TA de camundongos SAMP 6 não tenha sido observada, uma vez que essa linhagem de camundongos apresenta aumento do comprimento do telômero e da expressão e da atividade da telomerase, ao contrário das ratas utilizadas no presente estudo que, com cinco meses de idade, já apresentam redução da expressão de telomerase (39).…”

“…Além disso, ao contrário do estudo de Mirsaidi e cols. (50) no qual a osteoporose é decorrente de manipulação genética, no presente estudo, a osteoporose foi induzida pela deficiência dos esteroides sexuais, que é a causa mais frequente de osteoporose na mulher e que direta ou indiretamente pode afetar a diferenciação osteogênica das CTM (51). Dessa forma, a deficiência dos hormônios sexuais pode não ser o único fator que diminui a diferenciação osteogê-nica das CTM-TA de ratas OVX, já que existem outros fatores como vitamina D (10), ácido retinoico (10-12), BMP-2 (11-13), IGF-1 (14), TGF-β (15) e leptina (52) que influenciam a diferenciação osteogênica e que podem estar reduzidos em indivíduos com deficiência de esteroides sexuais (53,54).…”

Treatment of osteoarthritis with mesenchymal stem cells

“…Compared with BM-MSCs, A-MSCs are more easily cultured and grow more rapidly [50]. The main benefits of A-MSCs are that their proliferation and differen- [47] tiation potentials and telomerase are less affected by age than those of BM-MSCs [51].…”