Iohara Koichiro, Zheng Li, Wake Hiroaki, Ito Masataka, Nabekura Junichi, Wakita Hideaki, Nakamura Hiroshi, Into Takeshi, Matsushita Kenji, Nakashima Misako
Department of Oral Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Stem Cells. 2008 Sep;26(9):2408-18. doi: 10.1634/stemcells.2008-0393. Epub 2008 Jun 26.
Cell therapy with stem cells and endothelial progenitor cells (EPCs) to stimulate vasculogenesis as a potential treatment for ischemic disease is an exciting area of research in regenerative medicine. EPCs are present in bone marrow, peripheral blood, and adipose tissue. Autologous EPCs, however, are obtained by invasive biopsy, a potentially painful procedure. An alternative approach is proposed in this investigation. Permanent and deciduous pulp tissue is easily available from teeth after extraction without ethical issues and has potential for clinical use. We isolated a highly vasculogenic subfraction of side population (SP) cells based on CD31 and CD146, from dental pulp. The CD31(-);CD146(-) SP cells, demonstrating CD34+ and vascular endothelial growth factor-2 (VEGFR2)/Flk1+, were similar to EPCs. These cells were distinct from the hematopoietic lineage as CD11b, CD14, and CD45 mRNA were not expressed. They showed high proliferation and migration activities and multilineage differentiation potential including vasculogenic potential. In models of mouse hind limb ischemia, local transplantation of this subfraction of SP cells resulted in successful engraftment and an increase in the blood flow including high density of capillary formation. The transplanted cells were in proximity of the newly formed vasculature and expressed several proangiogenic factors, such as VEGF-A, G-CSF, GM-CSF, and MMP3. Conditioned medium from this subfraction showed the mitogenic and antiapoptotic activity on human umbilical vein endothelial cells. In conclusion, subfraction of SP cells from dental pulp is a new stem cell source for cell-based therapy to stimulate angiogenesis/vasculogenesis during tissue regeneration.
用干细胞和内皮祖细胞(EPCs)进行细胞治疗以刺激血管生成作为缺血性疾病的一种潜在治疗方法,是再生医学中一个令人兴奋的研究领域。EPCs存在于骨髓、外周血和脂肪组织中。然而,自体EPCs是通过侵入性活检获得的,这是一种可能会带来疼痛的操作。本研究提出了一种替代方法。恒牙和乳牙牙髓组织在拔牙后很容易获得,不存在伦理问题,并且具有临床应用潜力。我们从牙髓中基于CD31和CD146分离出了一个具有高度血管生成能力的侧群(SP)细胞亚群。CD31(-);CD146(-) SP细胞,表现为CD34+和血管内皮生长因子-2(VEGFR2)/Flk1+,与EPCs相似。这些细胞与造血谱系不同,因为不表达CD11b、CD14和CD45 mRNA。它们表现出高增殖和迁移活性以及多谱系分化潜能,包括血管生成潜能。在小鼠后肢缺血模型中,局部移植这个SP细胞亚群导致成功植入,并使血流增加,包括形成高密度的毛细血管。移植的细胞靠近新形成的脉管系统,并表达几种促血管生成因子,如VEGF-A、G-CSF、GM-CSF和MMP3。该亚群的条件培养基对人脐静脉内皮细胞显示出促有丝分裂和抗凋亡活性。总之,牙髓来源的SP细胞亚群是一种新的干细胞来源,用于基于细胞的治疗,以在组织再生过程中刺激血管生成/血管发生。
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