成體皮膚干細(xì)胞的研究對(duì)于治療燒傷、糖尿病引起的皮膚潰瘍,、皮膚衰老以及構(gòu)建人類組織工程皮膚都具有重要意義,。目前，應(yīng)用皮膚干細(xì)胞進(jìn)行組織工程學(xué)皮膚構(gòu)建以及皮膚疾病的治療尚處于初始階段,，但與此同時(shí),，臨床對(duì)于成體皮膚干細(xì)胞應(yīng)用的需求卻十分迫切。不同種類的皮膚干細(xì)胞在體外的自我更新以及分化能力的提高是目前急需解決的關(guān)鍵科學(xué)問題,。
8月出版的《衰老細(xì)胞》（Aging Cell）發(fā)表了中科院動(dòng)物研究所段恩奎研究員領(lǐng)導(dǎo)的胚胎生物學(xué)研究組最新完成的一項(xiàng)研究成果,。研究人員發(fā)現(xiàn)，真皮來源的干細(xì)胞在環(huán)境改變的情況下將發(fā)生細(xì)胞衰老（cellular senescence）現(xiàn)象,，并且這種現(xiàn)象最終將導(dǎo)致真皮干細(xì)胞自我更新能力的喪失,。不同年齡的真皮干細(xì)胞對(duì)這種細(xì)胞衰老的過程具有不同的抵抗能力。
該研究組的一系列實(shí)驗(yàn)表明,，真皮干細(xì)胞的衰老與PI3K-Akt信號(hào)通路具有密切的關(guān)系：應(yīng)用LY294002及Akt inhibitor VIII抑制該信號(hào)通路,，能夠迅速促使真皮干細(xì)胞進(jìn)入細(xì)胞衰老狀態(tài)；與之相反,，加入PDGF-AA以及bpv(pic)激活該通路則能夠有效地抑制真皮干細(xì)胞的衰老,，促進(jìn)其自我更新，并且不會(huì)影響該細(xì)胞的分化能力,。
該研究不僅為探索人類皮膚衰老的細(xì)胞分子機(jī)制奠定了基礎(chǔ),，并且為今后應(yīng)用成體皮膚干細(xì)胞進(jìn)行組織工程皮膚的構(gòu)建以及應(yīng)用再生醫(yī)學(xué)與轉(zhuǎn)化醫(yī)學(xué)進(jìn)行皮膚相關(guān)疾病的治療提供了理論依據(jù)與技術(shù)支持,。該研究得到了中國科學(xué)院戰(zhàn)略性先導(dǎo)科技專項(xiàng)與國家“發(fā)育與生殖研究”重大科學(xué)研究計(jì)劃等基金的資助。該論文共同第一作者是助理研究員劉爽博士和博士生劉恕,。(生物谷 Bioon.com)
doi: 10.1111/j.1474-9726.2011.00704.x
PMC:
PMID:
The PI3K‐Akt pathway inhibits senescence and promotes self‐\renewal of human skin‐derived precursors in vitro
Liu, Shuang; Liu, Shu; Wang, Xinyue; Zhou, Jiaxi; Cao, Yujing; Wang, Fei; Duan, Enkui
Keywords:skin‐derived precursors;PI3K‐Akt;self‐\renewal;cellular senescence;adult stem cells;PTENSummarySkin‐derived precursors (SKPs) are embryonic neural crest‐ or somite‐derived multipotent progenitor cells with properties of dermal stem cells. Although a large number of studies deal with their differentiation ability and potential applications in tissue damage repair, only a few studies have concentrated on the regulation of SKP self‐\renewal. Here, we found that after separation from their physiological microenvironment, human foreskin‐derived SKPs (hSKPs) quickly senesced and lost their self‐\renewal ability. We observed a sharp decrease in Akt activity during this process, suggesting a possible role of the PI3K‐Akt pathway in hSKP maintenance in vitro. Blocking this pathway with several inhibitors inhibited hSKP proliferation and sphere formation and increased hSKP senescence. In contrast, activating this pathway with PDGF‐AA and a PTEN inhibitor, bpV(pic), promoted proliferation, improved sphere formation, and alleviated senescence of hSKPs, without altering their differentiation potential. Data also implied that this effect was associated with altered actions of FoxO3 and GSK‐3β. Our results suggest an important role of the PI3K‐Akt pathway in the senescence and self‐\renewal of hSKPs. These findings also provide a better understanding of the cellular mechanisms underlying hSKP self‐\renewal and stem cell senescence to allow more efficient expansion of hSKPs for regenerative medical applications.
