Systematic assessment in an animal model of the angiogenic potential of different human cell sources for therapeutic revascularization.
Systematic assessment in an animal model of the angiogenic potential of different human cell sources for therapeutic revascularization.
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DOI：
10.1186/scrt114
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发表时间：
2012-07-03
影响因子：
7.5
通讯作者：
Turner ML
中科院分区：
文献类型：
--
作者：
Barclay GR;Tura O;Samuel K;Hadoke PW;Mills NL;Newby DE;Turner ML
最近在人外周血中循环的表达CD 34的细胞的小群体中鉴定了能够启动或增强血管生长的内皮祖细胞（EPC），并且其被认为是造血祖细胞（HPC）。此后不久，人HPC开始在临床试验中用作治疗性血管再生的EPC来源，特别是在心肌和严重肢体缺血中。然而，与造血功效与植入的CD 34+细胞数量定量相关的HPC不同，对于如何测量EPC或如何评估细胞移植物对血管再生的效力尚未达成共识。我们采用了自发性新生血管形成的动物模型，同时确定人类细胞是否纳入新的血管，并量化不同的推定血管生成细胞对血管形成的血管生成的数量方面的影响。我们系统地比较了不同来源的具有假定血管生成潜力的人细胞的治疗性血管生成能力，以开始为优化这种治疗的细胞采购提供一些基本原理。所用的人细胞是来自正常外周血和富含HPC的细胞来源（脐带血、动员外周血、骨髓）的单核细胞、这些细胞的CD34+富集或耗尽的亚群以及来自这些细胞的生长细胞群。建立了海绵植入物血管生成模型，以确定不同的人细胞对免疫缺陷小鼠中植入物血管生成的影响。通过免疫组化检测血管密度和来源物种来定量血管生成。动员的外周血或脐带血HPC的CD34+细胞是唯一促进新血管生长的细胞，但不掺入血管。只有内皮生长细胞（EOC）纳入血管，但这些并不促进血管生长。这些研究表明，由于EPC非常罕见，因此HPC在治疗性血管再生中的临床试验中观察到的任何益处主要是由间接促血管生成作用介导的，而不是通过直接掺入这些来源中包含的任何罕见EPC。应该有可能产生用于治疗用途的自体EOC，并评估EPC与HPC疗法的促血管生成作用不同或协同的作用。
Endothelial progenitor cells (EPC) capable of initiating or augmenting vascular growth were recently identified within the small population of CD34-expressing cells that circulate in human peripheral blood and which are considered hematopoietic progenitor cells (HPC). Soon thereafter human HPC began to be used in clinical trials as putative sources of EPC for therapeutic vascular regeneration, especially in myocardial and critical limb ischemias. However, unlike HPC where hematopoietic efficacy is related quantitatively to CD34+ cell numbers implanted, there has been no consensus on how to measure EPC or how to assess cellular graft potency for vascular regeneration. We employed an animal model of spontaneous neovascularization to simultaneously determine whether human cells incorporate into new vessels and to quantify the effect of different putative angiogenic cells on vascularization in terms of number of vessels generated. We systematically compared competence for therapeutic angiogenesis in different sources of human cells with putative angiogenic potential, to begin to provide some rationale for optimising cell procurement for this therapy. Human cells employed were mononuclear cells from normal peripheral blood and HPC-rich cell sources (umbilical cord blood, mobilized peripheral blood, bone marrow), CD34+ enriched or depleted subsets of these, and outgrowth cell populations from these. An established sponge implant angiogenesis model was adapted to determine the effects of different human cells on vascularization of implants in immunodeficient mice. Angiogenesis was quantified by vessel density and species of origin by immunohistochemistry. CD34+ cells from mobilized peripheral blood or umbilical cord blood HPC were the only cells to promote new vessel growth, but did not incorporate into vessels. Only endothelial outgrowth cells (EOC) incorporated into vessels, but these did not promote vessel growth. These studies indicate that, since EPC are very rare, any benefit seen in clinical trials of HPC in therapeutic vascular regeneration is predominantly mediated by indirect proangiogenic effects rather than through direct incorporation of any rare EPC contained within these sources. It should be possible to produce autologous EOC for therapeutic use, and evaluate the effect of EPC distinct from, or in synergy with, the proangiogenic effects of HPC therapies.
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影响因子：
20.1
作者：
Barcelos LS;Duplaa C;Kränkel N;Graiani G;Invernici G;Katare R;Siragusa M;Meloni M;Campesi I;Monica M;Simm A;Campagnolo P;Mangialardi G;Stevanato L;Alessandri G;Emanueli C;Madeddu P
通讯作者：
Madeddu P
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
2.9
作者：
Jaime-Perez, Jose Carlos;Guillermo-Villanueva, Victor A.;Gomez-Almaguer, David
通讯作者：
Gomez-Almaguer, David
影响因子：
4.4
作者：
Peebo, Beatrice Bourghardt;Fagerholm, Per;Lagali, Neil
通讯作者：
Lagali, Neil
影响因子：
3.6
作者：
Fuchs, Sabine;Hermanns, Maria Iris;Kirkpatrick, Charles James
通讯作者：
Kirkpatrick, Charles James