美國(guó)加州大學(xué)洛杉磯分?？茖W(xué)家們純化出在脂肪組織中發(fā)現(xiàn)的一小部分干細(xì)胞，并利用它們制造出骨組織,，并且形成的骨組織比利用傳統(tǒng)方法培養(yǎng)出的骨組織要更快速而且質(zhì)量更高,。這一發(fā)現(xiàn)可能有朝一日消除人們對(duì)令人痛苦的骨組織移植的需求。2012年6月11日,，相關(guān)研究論文在線發(fā)表在Stem Cells Translational Medicine期刊上,。
論文共同通訊作者、加州大學(xué)洛杉磯分校整形和重建外科部門研究副主席Chia Soo博士說(shuō),，脂肪組織被認(rèn)為是間充質(zhì)干細(xì)胞的一種理想的來(lái)源,，能夠產(chǎn)生骨、軟骨,、肌組織和其他組織,。同時(shí)脂肪組織比較豐富，容易通過(guò)諸如吸脂術(shù)等方法獲得,。另一名共同通訊作者為Bruno Péault博士,。
Péaul和 Soo領(lǐng)導(dǎo)的研究團(tuán)隊(duì)利用一種細(xì)胞分選機(jī)(cell sorting machine)從脂肪組織中分離和純化出人血管周干細(xì)胞(perivascular stem cells, hPSCs)，并且發(fā)現(xiàn)這些干細(xì)胞要比利用脂肪基質(zhì)血管組分(stromal vascular fraction,SVF)培養(yǎng)的細(xì)胞更好地構(gòu)建出骨組織,。他們還發(fā)現(xiàn)一種被稱作NELL-1的生長(zhǎng)因子在他們的模式動(dòng)物中能夠加強(qiáng)骨組織形成,。
在模式動(dòng)物中，Péaul和 Soo領(lǐng)導(dǎo)的研究團(tuán)隊(duì)將hPSCs和NELL-1植入肌袋(muscle pouc)中,，其中肌袋通常是不生長(zhǎng)骨組織的地方,。他們?nèi)缓罄肵射線來(lái)確定這些細(xì)胞的確產(chǎn)生骨組織。
Soo說(shuō),，如果一切順利的話,，那么病人可能有朝一日能夠快速獲得高質(zhì)量的骨組織移植材料：醫(yī)生們獲得他們的脂肪組織，并且從中純化出hPSCs,，然后將他們自己的干細(xì)胞和NELL-1移植到需要骨組織的地方,，而在NELL-1存在下，hPSCs有可能在病人體內(nèi)生長(zhǎng)成骨組織,。這一過(guò)程的目標(biāo)就是分離出hPSCs,，并加入含有NELL-1的基質(zhì)(matrix)或支架(scaffold)來(lái)協(xié)助細(xì)胞在不到一個(gè)小時(shí)之內(nèi)就黏附上來(lái)。
Péault說(shuō),，“令人興奮的是,，最近的研究已經(jīng)證實(shí)利用血管周干細(xì)胞來(lái)再生不同類型的組織，包括骨骼肌,、肺和甚至心肌,。進(jìn)一步的研究將拓展我們的發(fā)現(xiàn),，并利用hPSCs的強(qiáng)健性成骨潛能來(lái)治愈骨組織缺陷。”(生物谷 Bioon.com)
doi:10.5966/sctm.2012-0002
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Perivascular Stem Cells: A Prospectively Purified Mesenchymal Stem Cell Population for Bone Tissue Engineering
Aaron W. James, Janette N. Zara, Xinli Zhang Asal Askarinam, Raghav Goyal, Michael Chiang, Wei Yuan, Le Chang, Mirko Corselli, Jia Shen, Shen Pang, David Stoker, Ben Wug, Kang Ting, Bruno Péault and Chia Soo
Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering: it is largely dispensable and readily accessible with minimal morbidity. However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. In the present study, we prospectively purified human perivascular stem cells (PSCs) from adipose tissue and compared their bone-forming capacity with that of traditionally derived SVF. PSCs are a population (sorted by fluorescence-activated cell sorting) of pericytes (CD146+CD34−CD45−) and adventitial cells (CD146−CD34+CD45−), each of which we have previously reported to have properties of mesenchymal stem cells. Here, we found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. We next sought to optimize PSCs for in vivo bone formation, adopting a demineralized bone matrix for osteoinduction and tricalcium phosphate particle formulation for protein release. Patient-matched, purified PSCs formed significantly more bone in comparison with traditionally derived SVF by all parameters. Recombinant bone morphogenetic protein 2 increased in vivo bone formation but with a massive adipogenic response. In contrast, recombinant Nel-like molecule 1 (NELL-1; a novel osteoinductive growth factor) selectively enhanced bone formation. These studies suggest that adipose-derived human PSCs are a new cell source for future efforts in skeletal regenerative medicine. Moreover, PSCs are a stem cell-based therapeutic that is readily approvable by the U.S. Food and Drug Administration, with potentially increased safety, purity, identity, potency, and efficacy. Finally, NELL-1 is a candidate growth factor able to induce human PSC osteogenesis.
