Systemic transplantation of adult multipotent stem cells prevents articular cartilage degeneration in a mouse model of accelerated ageing.
Systemic transplantation of adult multipotent stem cells prevents articular cartilage degeneration in a mouse model of accelerated ageing.
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DOI：
10.1186/s12979-021-00239-8
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发表时间：
2021-06-07
期刊：
影响因子：
--
通讯作者：
Lavasani M
中科院分区：
文献类型：
--
作者：
Thompson SD;Pichika R;Lieber RL;Lavasani M
骨关节炎（OA）是老年人最常见的关节疾病之一，也是全球残疾的主要原因。衰老是导致OA的关节软骨（AC）退化的主要风险因素，并且与年龄相关的再生能力下降加速了OA的进展。在这里，我们证明了从年轻的野生型小鼠中分离的独特的成体多能肌肉源性干/祖细胞（MDSPC）群体全身移植到Zmpste 24 −/−小鼠（Hutchinson-Gilford早衰综合征的模型，一种以加速衰老为标志的疾病）中，可以预防与衰老相关的AC稳态下降。MDSPC治疗抑制软骨降解因子如促炎细胞因子和细胞外基质蛋白酶的表达，而与软骨机械支持和拉伸强度、软骨弹性、软骨细胞增殖和分化以及软骨生长相关的促再生标志物增加。值得注意的是，MDSPC移植还增加了已知在免疫调节、自噬、抗应激、促长寿和端粒保护中起关键作用的基因的表达水平。我们的研究结果还表明，MDSPC移植增加蛋白多糖含量调节软骨细胞增殖。总之，这些发现证明了全身移植的年轻MDSPC在早老性AC中保持健康的稳态并在分子和组织水平上促进组织再生的能力。这些结果强调了全身递送的多能成体干细胞预防年龄相关性AC变性的治疗潜力。在线版本包含补充材料，可通过10.1186/s12979-021-00239-8获得。
Osteoarthritis (OA) is one of the most prevalent joint diseases of advanced age and is a leading cause of disability worldwide. Ageing is a major risk factor for the articular cartilage (AC) degeneration that leads to OA, and the age-related decline in regenerative capacity accelerates OA progression. Here we demonstrate that systemic transplantation of a unique population of adult multipotent muscle-derived stem/progenitor cells (MDSPCs), isolated from young wild-type mice, into Zmpste24−/− mice (a model of Hutchinson-Gilford progeria syndrome, a condition marked by accelerated ageing), prevents ageing-related homeostatic decline of AC. MDSPC treatment inhibited expression of cartilage-degrading factors such as pro-inflammatory cytokines and extracellular matrix-proteinases, whereas pro-regenerative markers associated with cartilage mechanical support and tensile strength, cartilage resilience, chondrocyte proliferation and differentiation, and cartilage growth, were increased. Notably, MDSPC transplantation also increased the expression level of genes known for their key roles in immunomodulation, autophagy, stress resistance, pro-longevity, and telomere protection. Our findings also indicate that MDSPC transplantation increased proteoglycan content by regulating chondrocyte proliferation. Together, these findings demonstrate the ability of systemically transplanted young MDSPCs to preserve a healthy homeostasis and promote tissue regeneration at the molecular and tissue level in progeroid AC. These results highlight the therapeutic potential of systemically delivered multipotent adult stem cells to prevent age-associated AC degeneration. The online version contains supplementary material available at 10.1186/s12979-021-00239-8.
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影响因子：
7.5
作者：
Gharaibeh B;Lavasani M;Cummins JH;Huard J
通讯作者：
Huard J
影响因子：
13.6
作者：
Freund A;Orjalo AV;Desprez PY;Campisi J
通讯作者：
Campisi J
影响因子：
5.6
作者：
Krajewska-Włodarczyk M;Owczarczyk-Saczonek A;Placek W;Osowski A;Wojtkiewicz J
通讯作者：
Wojtkiewicz J
影响因子：
3.3
作者：
Deasy, BM;Gharaibeh, BM;Huard, J
通讯作者：
Huard, J
DOI：
10.1073/pnas.192460799
发表时间：
2002-10-01
影响因子：
11.1
作者：
Bergo, MO;Gavino, B;Young, SG
通讯作者：
Young, SG