台湾荣民总医院最近利用缺氧的环境培养人类骨髓间叶性干细胞，取得了突破性的研究成果。阳明大学临床医学研究所教授、荣民总医院骨科部主治医师洪士杰十日举行新闻发布会，公布了这一成果。

   动物实验虽证实移植骨髓间叶细胞可促进人体组织的修复与再生，但却发现其在移植后着床于接受者的比率很低，因此使得这种干细胞移植的治疗效果受到质疑。洪士杰与美国杜兰大学同行的合作研究发现，缺氧状态下培养的间叶干细胞可增加移植后着床的成功率。在移植前将间叶干细胞放置于百分之一氧气培养四十八小时，移植后着床的细胞数可增加三倍，大大提高了移植的成功率。

   洪士杰还发现，间叶干细胞可存活于缺氧状况并继续增殖，但一般的已分化细胞却会因缺氧凋亡。他举血管内皮细胞为例说，间叶干细胞可拯救血管内皮细胞因缺氧所造成的死亡，同时可促进血管内皮细胞形成血管。干细胞会释放生长因子及激素，包括血管内皮增生因子及第六型介白质，这些因子可以经由相关讯息传递路径来抑制血管内皮细胞的凋亡及促进血管新生。

   洪士杰说，这个研究证实了人类骨髓间叶干细胞可分泌生长因子及激素来促进人体组织的修复与再生。使干细胞的应用将不受限于应用细胞治疗造成着床及分化的机制来促进组织修复，同时也能应用其分泌因子来帮助组织再生。分离纯化干细胞的分泌因子并加以应用，将有助于血管新生，并可用于治疗因血流不足而造成的心肌梗塞、中风及缺血肢体等疾病。

   相关研究已发表在最新一期的国际干细胞权威期刊《干细胞》上。（援引中新网）

原始出处:

Stem CellsVol. 25 No. 9 September 2007, pp. 2363 -2370
doi:10.1634/stemcells.2006-0686;www.StemCells.com

TRANSLATIONAL AND CLINICAL RESEARCH: MESENCHYMAL STEM CELLS SERIES

Angiogenic Effects of Human Multipotent Stromal Cell Conditioned Medium Activate the PI3K-Akt Pathway in Hypoxic Endothelial Cells to Inhibit Apoptosis, Increase Survival, and Stimulate Angiogenesis

Shih-Chieh Hunga,b,c, Radhika R. Pochampallya, Sy-Chi Chenb, Shu-Ching Hsua, Darwin J. Prockopa

aCenter for Gene Therapy, Tulane University Health Science Center, New Orleans, Louisiana, USA;
bStem Cell Laboratory, Veterans General Hospital-Taipei, Taipei, Taiwan;
cInstitute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

Key Words. Bone marrow stromal cells • Hypoxia • Endothelial cell • Angiogenesis • Apoptosis • Human aortic endothelial cells Interleukin-6 • Therapeutic potential

Correspondence: Darwin J. Prockop, Ph.D., M.D., Center for Gene Therapy, Tulane University Health Sciences Center, 1430 Tulane Avenue, SL-99, New Orleans, Louisiana 70112, USA. Telephone: (504) 988-7711; Fax: (504) 988-7710; e-mail:dprocko@tulane.edu; or Shih-Chieh Hung, Ph.D., M.D., Department of Medical Research and Education, Veteran General Hospital-Taipei, 201, Sec2, Shih-Pai Road, Taipei, Taiwan. Telephone: 886-2-28757396; Fax: 886-2-28757396; e-mail:hungsc@vghtpe.gov.tw

Received October 26, 2006; accepted for publication May 18, 2007.
First May 31, 2007. published online in STEM CELLS EXPRESS 

Recent reports indicated that vascular remodeling and angiogenesis are promoted by conditioned medium from the cells referred to as multipotent stromal cells (MSCs). However, the molecular events triggered by MSC-conditioned medium (CdM) were not defined. We examined the effects of CdM from human MSCs on cultures of primary human aortic endothelial cells (HAECs). The CdM inhibited hypoxia-induced apoptosis and cell death of HAECs. It also promoted tube formation by HAECs in an assay in vitro. Conditioned medium from multipotent stromal cells incubated under hypoxic conditions in serum-free endothelial basal medium for 2 days (CdMHyp) from hypoxic culture of MSCs was more effective than conditioned medium from MSCs incubated under normoxic conditions in serum-free endothelial basal medium for 2 days from normoxic cultures of MSCs, an observation in part explained by its higher content of antiapoptotic and angiogenic factors, such as interleukin (IL)-6, vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein (MCP)-1. The effects of CdMHyp on hypoxic HAECs were partially duplicated by the addition of IL-6 in a dose-dependent manner; however, anti-IL-6, anti-MCP-1, and anti-VEGF blocking antibodies added independently did not attenuate the effects. Also, addition of CdMHyp activated the PI3K-Akt pathway; the levels of p-Akt and several of its downstream targets were increased by CdMHyp, and both the increase in p-Akt and the increase in angiogenesis were blocked by an inhibitor of PI3K-Akt or by expression of a dominant negative gene for PI3K. CdMHyp also increased the levels of p-extracellular signal-regulated kinase (ERK), but there was a minimal effect on p-signal transducer and activator of transcription-3, and an inhibitor of the ERK1/2 pathway had no effect on hypoxia-induced apoptosis of the HAECs. The results are consistent with suggestions that administration of MSCs or factors secreted by MSCs may provide a therapeutic method of decreasing apoptosis and enhancing angiogenesis.

Disclosure of potential conflicts of interest is found at the end of this article.

                                          摘自《生物谷》