脐带血干细胞：组织工程人工心脏研究种子细胞的新来源*

背景：脐带血干细胞富含多种干/祖细胞,其各种干/祖细胞移植治疗和作为种子细胞在组织工程领域的研究成为当前的热点。 目的：综述脐带血干细胞中存在的多种干/祖细胞的生物学特性及在心脏疾病的实验应用和脐带血干细胞在心脏疾病的实验应用。 方法：应用计算机检索1999-01/2009-10中国数字图书馆、维普期刊数据库相关文章,检索词为“脐带血干细胞,造血干/祖细胞,间充质干细胞,内皮祖细胞,内皮细胞,心肌细胞,组织工程,种子细胞”,并限定文章语言种类为中文。同时计算机检索1999-01/2009-10 PubMed 数据库相关文章,检索词为“umbilical cord blood stem cells,hematopoietic progenitor cells/hematopoietic stem cells,mesenchymal stem cells,endothelial progenitor cells,endothelial cells,myocardial cells,tissue engineering,seeded cells”,并限定文章语言种类为English。同时手工检索《干细胞生物学》专著,共检索到文献95篇。根据纳入标准最终纳入文献30篇。 结果与结论：脐带血干细胞是一种成体多能干细胞,富含造血干/祖细胞、间充质干细胞、内皮祖细胞、非限制性体干细胞等。相对于骨髓干细胞和外周血干细胞,脐带血干细胞来源丰富,获得更为容易,更为原始,分化增殖能力更强,排斥反应小,在体外可以分化为血管内皮细胞、心肌细胞等多种细胞。基于脐带血干细胞独特的生物特性、资源优势及在冠心病和缺血性心肌病的治疗上取得了一定的成果,为构建组织工程人工心脏的种子细胞来源提供可能,在心脏再生和组织工程人工心脏方面的应用展示了广阔的前景。     

干细胞疗法治疗缺血性卒中的研究进展

目前缺血性卒中所致神经损伤修复的传统治疗方法尚无突破,而以干细胞为基础的新型治疗策略正成为研究热点。大量动物实验和部分临床实验已经证实,无论是机体自身干、祖细胞的动员、募集,还是自体或异体干细胞移植,都显著改善了受损的神经功能。目前已证实局部植入、静脉注入、或全身动员的干细胞在基质细胞衍生因子-1/基质细胞衍生因子-1受体4（Stromal cell-derived Factor-1/CXC Chemokine Receptor-4,SDF-1/CXCR4）趋化分子和β2-整联蛋白等因子的作用下归巢至脑缺血区域;提供富含营养因子的微环境,保护坏死灶周围缺血半暗带组织;增强血管发生和血管生成;促进卒中后内源性干、祖细胞的迁移、存活和分化;并逐渐分化为神经细胞替代丢失的神经元。这几重因素可能共同参与了结构重建和功能修复。     

血管内皮祖细胞在组织工程皮肤构建中的意义

背景：血管内皮祖细胞可加速缺血部位的血管化。 目的：综合分析血管内皮祖细胞加速组织工程皮肤血管化的方法和途径。 方法：计算机检索中国期刊全文数据及PubMed数据库1999-09/2009-09相关文章，检索词为“血管内皮祖细胞，组织工程皮肤，血管新生，endothelial progenitor cell(EPC)，tissue engineered skin，vascularization ”。纳入与血管内皮祖细胞与组织工程皮肤研究现状与发展密切相关文章，包括：①血管内皮祖细胞的生物学特性、动员方法及促进血管新生的可能机制。②组织工程皮肤的应用现状。③组织工程皮肤中血管内皮祖细胞的研究现状。 结果与结论：血管内皮祖细胞是指特异性归巢于血管新生组织，并能分化增生为成熟内皮细胞的一群祖细胞。近年来大量的动物实验证实，通过移植体外培养的血管内皮祖细胞到肢体缺血部位，可以加速缺血部位的血管化。在心肌梗死方面已经进行了自体血管内皮祖细胞治疗心肌梗死的临床试验，使其临床应用逐渐成为可能。而目前构建的组织工程皮肤中缺少血管成分，严重影响人工皮肤中活细胞的存活及其功能实现，如何构建出含有血管的人工皮肤及加速人工真皮替代物血管化引起了广大的关注。应用血管内皮祖细胞促进组织工程皮肤血管化进而提高其成活率有重要的临床意义。     

转染血管内皮细胞生长因子骨髓间充质干细胞与牛松质骨支架复合组织工程骨的血管形成

背景：小块组织工程骨植入动物体内后,早期依靠组织液的渗透可获得营养,但大块组织工程骨的营养仅靠组织液的渗透是远远不够的,必须通过血管再生来获得。 目的：观察转染血管内皮细胞生长因子表达载体骨髓间充质干细胞复合组织工程骨植入动物体内后的血管形成能力。 方法：制作日本大耳白兔双侧尺骨中段骨缺损模型,左侧尺骨缺损植入转染血管内皮细胞生长因子表达载体的自体骨髓间充质干细胞复合脱钙脱脂去蛋白的牛松质骨支架组织工程骨为实验组,右侧尺骨缺损植入自体骨髓间充质干细胞复合脱钙脱脂去蛋白的牛松质骨支架组织工程骨为对照组。术后12周行X射线摄片观察、大体标本观察、苏木精-伊红染色和Masson染色组织切片观察、MiFas图像分析系统定量分析。 结果与结论：实验组与对照组尺骨缺损处均有连续骨痂形成;组织切片经苏木精-伊红染色、Masson三色法染色及MiFas图像分析系统定量分析可见实验组和对照组均有大量的新生骨,但实验组新生血管明显多于对照组(P < 0.01),且血管较粗大,而且与新生骨接近。说明将转染血管内皮细胞生长因子表达载体的骨髓间充质干细胞复合在组织工程骨上植入动物体内可明显促进新生血管的形成。     

组织工程血管的种子细胞

血管移植物数量和功能的不足制约着许多疾病的治疗，因此组织工程血管成为研究的热点。种子细胞作为组织工程血管重要组成部分，如何达到正常血管内皮细胞及平滑肌细胞的生理功能，是人们关注的焦点。干细胞因具备多向分化潜能，被视为理想的种子细胞，然而干细胞种类较多，在组织工程血管的构建过程中，哪种干细胞更适合作为种子细胞，尚无定论。文章对造血干细胞、骨髓间充质干细胞、脂肪干细胞等多种干细胞进行比较，简述各自的特点，试图全面了解干细胞的功能，为进一步实验奠定一定的基础。     

成体干细胞向血管内皮细胞定向分化的研究现状

成体干细胞存在于已分化的组织器官中，具有明显的可塑性，能跨系统、跨胚层分化，在组织工程和损伤修复领域具有重要的应用价值。在血管组织工程研究领域中，成体干细胞作为种子细胞得到越来越广泛而深入的研究。目前研究表明，具有向血管内皮细胞分化的成体干细胞主要有骨髓间充质干细胞、造血干细胞、脂肪来源的干细胞以及羊膜来源的干细胞等。基于此，就成体干细胞作为种子细胞在血管组织工程领域研究现状进行综述。     

神经组织工程研究进展

组织工程近年来不仅在软骨、骨、皮肤、肌腱、血管组织等方面取得了蓬勃发展,而且随着可降解材料的研制和开发、神经干细胞研究的深入,神经组织工程研究也取得了一定的进展。本文就神经组织工程中种子细胞、支架材料和细胞因子等方面的研究作一综述。种子细胞种子细胞的培养是组织工程的基本要素,细胞主要来源于自体、同种异体、异种组织细胞等。神经组织工程的种子细胞主要为雪旺细胞和神经干细胞。1.雪旺细胞雪旺细胞(Schwann cells,SCs)是周围神经的主要结构和功能细胞,是周围神经组织工程研究的重要种子细胞。SCs在周围神经修复中起着…     

VIP/70005/骨髓间充质干细胞在膀胱组织工程中应用与生物支架材料性能评价

背景：利用肠道进行膀胱的修复和重建仍是进行膀胱替代的金标准。但是,由于肠道处在泌尿系的环境中,可能会引起代谢紊乱、感染、结石形成甚至恶变等一系列并发症。 目的：总结评价骨髓间充质干细胞在膀胱组织工程中应用,评价其生物支架材料性能。以寻找合理的膀胱替代物。 方法：以 “组织工程,膀胱,间充质干细胞,支架” 为中文关键词, “tissue engineering,Bladder, Mesenchymal stem cells” 为英文关键词,采用计算机检索1993-01/2009-10相关文章。纳入与有关种子细胞与组织工程膀胱相关及与膀胱生物支架材料相关的文章;排除重复研究或Meta分析类文章。以29篇文献为主,重点对一下5个问题进行了讨论：①如何稳定可靠迅速地获取充足的有活力的细胞源？②膀胱生物支架材料方面的选择? ③修复重建膀胱的组织工程技术选择？④伦理学问题。⑤如何促进体外构建的膀胱组织植入体内后的快速血管化？ 结果与结论：采用自体间充质干细胞作为种子细胞应用于膀胱组织工程, 不仅取材方便、具有低免疫原性, 而且还可能分化为构建膀胱组织所必须的移行上皮细胞和平滑肌细胞以及血管内皮细胞、神经细胞从而改善再生组织的血供和神经功能, 并能避免移植物纤维化挛缩, 显示其独特的优越性,具有广阔的发展前景。但是,组织工程膀胱用于临床的有效性尚有待进一步评估,如组织工程膀胱与自体膀胱组织的愈合、结构和功能的重塑、血管化及神经支配的建立、伦理问题等重大难题都需要进一步研究。     

脂肪源性干细胞生物学特性及在组织工程中的应用

背景：脂肪源性干细胞具有自我更新及多向分化潜能,在体外适当的诱导条件下可向脂肪细胞、成骨细胞、软骨细胞、心肌细胞、神经细胞和肝细胞等多种细胞分化,在组织工程中具有良好的应用前景。 目的：了解脂肪源性干细胞的生物学特征及其在组织工程中的应用。 方法：以“tissue-derived stem cells,tissue engineering,脂肪,间充质干细胞,组织工程”为关键词检索Elsevier数据库2000-01/2010-05与中国期刊全文数据库2000-01/2010-05相关文章。 结果与结论：脂肪源性干细胞增殖速度快,取材方便、材料来源广,并且能自体取材,避免了免疫排斥问题。目前尚未找到鉴定脂肪源性干细胞的金标准,但研究者采用流式细胞仪和免疫组织化学方法研究发现体外培养的脂肪源性干细胞具有间充质干细胞这一类细胞的特异性表面标记。脂肪源性干细胞可向脂肪、骨、软骨、肌肉、造血、肝和神经等多种细胞分化。组织或器官缺损性疾病、退行性疾病及遗传性疾病可尝试通过组织工程技术将组织来源的干细胞与支架材料复合移植入体内,来解决这一临床难题已成为研究热点。     

带部分松质骨小牛皮质骨支架复合兔骨髓间充质干细胞植入兔体内血管内皮细胞生长因子的表达

摘要 背景：目前异种松质骨作为组织工程材料较为多见,而皮质骨因其难以降解,孔隙率低等原因限制了其使用。但皮质骨具有许多松质骨不具备的优越性,如生物力学方面,如何开发利用皮质骨是课题研究的重点。 目的：观察兔骨髓间充质干细胞复合带部分松质骨小牛皮质骨支架材料植入兔体内后血管内皮细胞生长因子表达。 方法：健康1月龄新西兰大白兔4只用于干细胞提取;3月龄新西兰大白兔60只,在髂骨翼分别植入骨髓间充质干细胞成骨诱导后复合异种骨,单纯异种骨,自体髂骨。术后4,8,12,24周取材RT-PCR检测血管内皮细胞生长因子的表达。 结果与结论：血管内皮细胞生长因子的表达情况：在各时间点,单纯异种骨组低于骨髓间充质干细胞成骨诱导后复合异种骨组和自体髂骨组(P < 0.05)。术后第4周时,骨髓间充质干细胞成骨诱导后复合异种骨组低于自体髂骨组(P < 0.05),在术后第8,12,24周时,两组差异无显著性意义(P > 0.05)。提示兔骨髓间充质干细胞复合带部分松质骨的小牛皮质骨支架材料植入新西兰兔体内具有较好的血管生成能力。 关键词：成骨诱导;骨髓间充质干细胞;带部分松质骨小牛皮质骨;血管内皮细胞生长因子;骨科生物材料 doi:10.3969/j.issn.1673-8225.2010.34.005     

尿路组织工程材料的血管化*☆

学术背景：组织材料血管化是组织工程学中重要的组成部分之一,复合材料的血管化对复合其上的细胞存活以及原有组织或器官功能的恢复起到至关重要的作用。 目的：结合近年来的相关文献,对尿路组织工程修复重建中血管化的研究做一综述。 检索策略：由第一作者应用计算机检索PUBMED,中国期刊数据库 2002-07/2007-10相关文章,检索词为“tissue engineering, vascularization, angiogenesis, omentum, growth factor, endothelial progenitor cell, urethra,bladder,urology”或“组织工程,血管化,尿道,膀胱,生长因子,网膜,血管内皮组细胞,尿路”,文章语言种类为“English”或中文。纳入标准：内容应与泌尿系统组织修复重建材料血管化的研究相关。排除标准：重复文章。 文献评价：共收集到214篇相关文献,82篇符合纳入标准,其中31篇涉及网膜在泌尿系统血管化中的应用,25篇涉及生长因子在泌尿系统组织工程重建中的研究,剩余26篇为种子细胞在泌尿系统血管化中的应用。选用具有代表性的30篇。 资料综合：目前已有研究利用网膜作为生物反应器对不同的支架材料进行包埋以重建输尿管和膀胱组织,并取得了满意的效果;还有利用血管内皮细胞生长因子、碱性成纤维细胞生长因子等相关生长因子与脱细胞基质进行复合促进了毛细血管的增生的研究;更有学者利用各种相关的种子细胞与支架材料复合构建具有微血管结构的替代材料。而从干细胞和相关祖细胞上对组织材料进行微血管化的构建将是泌尿系统组织替代材料血管化的发展方向。 结论： 利用多种手段进行材料血管化的研究是目前泌尿系统组织工程研究中的重点之一,但其研究尚处在起步阶段,多数报道仅处于实验室阶段,真正应用于临床的文献较少见。因而目前来说仍有许多关键点有待于解决。     

In search of the best candidate for regeneration of ischemic tissues: are embryonic/fetal stem cells more advantageous than adult counterparts?

Human stem cells and progenitor cells from the bone marrow have been proposed for the regeneration of ischemic cardiac tissues. Early clinical trials indicate that infusion of autologous bone-marrow cells into the infarcted heart enhances ventricular function, albeit the long-term benefit remains to be ascertained. Alternatively, angiogenic growth factors could be used to stimulate the recruitment of vascular progenitor cells into tissues in need of regeneration. Unfortunately, in atherosclerotic patients, the curative potential of autologous stem cells might be impoverished by underlying disease and associated risk factors. Thus, research is focusing on the use of embryonic stem cells which are capable of unlimited self-renewal and have the potential to give rise to all tissue types in the body. Ethical problems and technical hurdles may limit the immediate application of embryonic stem cells. In the meanwhile, fetal hematopoietic stem cells,which have been routinely used to reconstitute the hematopoietic system in man, could represent an alternative, owing to their juvenile phenotype and ability to differentiate into vascular endothelial, muscular, and neuronal cell lineages. With progresses in stem cell expansion, the blood of a single cord could be sufficient to transplant an adult. These observations raise the exciting possibility of using fetal cells as a new way to speed up the healing of damaged tissues.     

不同浓度细胞种植脱细胞血管基质上构建组织工程血管

摘要 背景：前期研究表明制备的脱细胞血管基质适合平滑肌细胞和内皮祖细胞生长,但是共培养模型中细胞接种密度对血管基质上细胞覆盖率的影响尚不清楚。 目的：观察不同浓度度细胞种植在脱细胞血管基质上的生长情况。 方法：采用两步法进行细胞种植,先将不同细胞浓度血管平滑肌细胞种植在脱细胞血管基质上,培养3 d后再将不同浓度内皮祖细胞接种在平滑肌细胞-血管基质复合体上,构建片状组织工程材料,分别在内皮祖细胞种植后3 d、1周时间段获取标本,扫描电镜观察细胞在材料上的生长情况。 结果与结论：血管平滑肌细胞和内皮祖细胞在脱细胞基质表面生长良好。不同浓度细胞在基质上的排布不同;提高接种的浓度有利于在材料表面快速形成致密的细胞层。提示采用两步法以合适的浓度种植细胞于脱细胞基质上,可以构建组织工程血管。 关键词：内皮祖细胞;平滑肌细胞;组织工程血管;脱细胞血管基质;种植 doi:10.3969/j.issn.1673-8225.2010.47.010     

人外周血内皮祖细胞培养方法的建立

背景：成人外周血来源丰富,但内皮祖细胞含量较少,为使其能够更好的应用于组织工程及细胞治疗,有必要建立外周血内皮祖细胞成熟、稳定的体外扩增体系。 目的：建立稳定的人外周血分离、培养和体外扩增血管内皮祖细胞的方法。 方法：应用密度梯度离心法,获取外周血单个核细胞,将分选后细胞接种于预先包埋了人纤维连接蛋白的培养板上,加入内皮祖细胞专用培养基中培养3 d后,洗掉非贴壁细胞,培养至第6天,收集贴壁细胞,应用倒置显微镜和苏木精-伊红染色进行细胞形态学观察;采用MTT法和细胞计数测定第1,3代细胞生长曲线;应用流式细胞仪测定祖细胞和内皮细胞系标志,对培养的细胞进行鉴定。 结果与结论：细胞生长曲线测定表明接种后第3天细胞进入指数增生期,至第6天进入平台期,随着传代次数的增加,细胞增殖速度变慢,同时表达干细胞表面标志CD34、CD133和内皮细胞表面标志血管性血友病因子、血管内皮生长因子受体2。证明人外周血可以分离培养内皮祖细胞。     

Platelet interaction with progenitor cells: potential implications for regenerative medicine

Circulating endothelial progenitor cells have been shown to instigate new vessel formation via angiogenesis and neovascularisation and to induce ongoing vascular and tissue repair by domiciliation to sites of vascular or tissue damage. However, the mechanisms that recruit circulating endothelial progenitor cells towards vascular lesions and regulate repair mechanisms of ischemic peripheral organs are poorly described. Domiciliation of endothelial progenitor cells in peripheral tissue is a multi-step cascade including initial adhesion to subendothelial matrix or endothelium, transmigration and invasion of the target tissue. Platelets are the first circulating blood cells that interact with the injured vessel wall. They contain a number of growth factors, chemokines, cytokines and adhesive proteins that are released or surface-expressed upon platelet activation including adhesion. Recent studies suggest that platelet interaction with endothelial progenitor cells influences chemotaxis, adhesion, activation and differentiation of progenitor cells. Release of the chemokine SDF-1 from platelets enhances neovascularization through mobilization of progenitor cells. Adherent platelets recruit bone marrow-derived progenitor cells to arterial thrombi in vitro and in vivo and induce their subsequent differentiation towards an endothelial phenotype. Moreover, platelet accumulation in a co-culture system with CD34(+) progenitor cells results in the differentiation of the latter to macrophages in vitro. Although further studies are needed to elucidate the mechanisms that platelets determine the fate of endothelial progenitor cells into vascular lesions, platelet interaction with progenitor cells seems to play a decisive role in vascular and tissue regeneration.     

Progress in clinical trials of cell transplantation for the treatment of spinal cord injury:how many questions remain unanswered?

Spinal cord injury can lead to severe motor,sensory and autonomic nervous dysfunctions.However,there is currently no effective treatment for spinal cord injury.Neural stem cells and progenitor cells,bone marrow mesenchymal stem cells,olfactory ensheathing cells,umbilical cord blood stem cells,adipose stem cells,hematopoietic stem cells,oligodendrocyte precursor cells,macrophages and Schwann cells have been studied as potential treatments for spinal cord injury.These treatments were mainly performed in animals.However,subtle changes in sensory function,nerve root movement and pain cannot be fully investigated with animal studies.Although these cell types have shown excellent safety and effectiveness in various animal models,sufficient evidence of efficacy for clinical translation is still lacking.Cell transplantation should be combined with tissue engineering scaffolds,local drug delivery systems,postoperative adjuvant therapy and physical rehabilitation training as part of a comprehensive treatment plan to provide the possibility for patients with SCI to return to normal life.This review summarizes and analyzes the clinical trials of cell transplantation therapy in spinal cord injury,with the aim of providing a rational foundation for the development of clinical treatments for spinal cord injury.     

Insights into stem cell therapy for diabetic retinopathy: a bibliometric and visual analysis

Stem cells have been confirmed to be involved in the occurrence and development of diabetic retinopathy; however, the underlying mechanisms remain unclear. In this study, we used Citespace software to visually analyze 552 articles exploring the stem cell-based treatment of diabetic retinopathy over the past 20 years, which were included in the Web of Science Core Collection. We found the following: (1) a co-citation analysis of the references cited by all 552 articles indicated 15 clusters. In cluster #0, representing the stem cell field, some highly cited landmark studies emerged between 2009–2013. For example, endothelial progenitor cells and diabetic retinopathy gradually received the full attention of scholars, in terms of their relationship and therapeutic prospects. Some researchers also verified the potential of adipose-derived stem cells to differentiate into stable retinal perivascular cells, using a variety of animal models of retinal vascular disease. All of these achievements provided references for the subsequent stem cell research. (2) An analysis of popular keywords among the 552 articles revealed that, during the past 20 years, a relative increase in basic research articles examining stem cells and endothelial progenitor cells for the treatment of diabetic retinopathy was observed. The contents of these articles primarily involved the expression of vascular endothelial growth factor, vascular regeneration, oxidative stress, and inflammatory response. (3) A burst analysis of keywords used in the 552 articles indicated that genetic and cytological research regarding the promotion of angiogenesis was an issue of concern from 2001 to 2012, including several studies addressing the expression of various growth factor genes; from 2014 to 2020, mouse models of diabetic retinopathy were recognized as mature animal models, and the most recent research has focused on macular degeneration, macular edema, neurodegeneration, and inflammatory changes in diabetic animal models. (4) Globally, the current authoritative studies have focused on basic research towards the stem cell treatment of diabetic retinopathy. Existing clinical studies are of low quality and have insufficient evidence levels, and their findings have not yet been widely accepted in clinical practice. Major challenges during stem cell transplantation remain, including stem cell heterogeneity, cell delivery, and the effective homing of stem cells to damaged tissue. However, clinical trials examining potential stem cell-based treatments of diabetic retinopathy, including the use of pluripotent stem cells, retinal pigment epithelial cells, bone marrow mesenchymal stem cells, and endothelial progenitor cells, are currently ongoing, and high-quality clinical evidence is likely to appear in the future, to promote clinical transformation.Key Words: diabetes, diabetic retinopathy, epithelial cells, macula, progenitor cells, retina, stem cells, visual analysis

Chinese Library Classification No. R453; R364.5; R741     

CNS stem and progenitor cell differentiation into functional neuronal circuits in three-dimensional collagen gels

The mammalian central nervous system (CNS) has little capacity for self-repair after injury, and neurons are not capable of proliferating. Therefore, neural tissue engineering that combines neural stem and progenitor cells and biologically derived polymer scaffolds may revolutionize the medical approach to the treatment of damaged CNS tissues. Neural stem and progenitor cells isolated from embryonic rat cortical or subcortical neuroepithelium were dispersed within type I collagen, and the cell-collagen constructs were cultured in serum-free medium containing basic fibroblast growth factor. The collagen-entrapped stem and progenitors actively expanded and efficiently generated neurons, which developed neuronal polarity, neurotransmitters, ion channels/receptors, and excitability. Ca2+ imaging showed that differentiation from BrdU+/TuJ1- to BrdU-/TuJ1+ cells was accompanied by a shift in expression of functional receptors for neurotransmitters from cholinergic and purinergic to predominantly GABAergic and glutamatergic. Spontaneous postsynaptic currents were recorded by patch-clamping from precursor cell-derived neurons and these currents were partially blocked by 10-microM bicuculline, and completely blocked by additional 10 microM of the kainate receptor antagonist CNQX, indicating an appearance of both GABAergic and glutamatergic synaptic activities. Staining with endocytotic marker FM1-43 demonstrated active synaptic vesicle recycling occurring among collagen-entrapped neurons. These results show that neural stem and progenitor cells cultured in 3D collagen gels recapitulate CNS stem cell development; this is the first demonstration of CNS stem and progenitor cell-derived functional synapse and neuronal network formation in a 3D matrix. The proliferative capacity and neuronal differentiating potential of neural progenitors in 3D collagen gels suggest their potential use in attempts to promote neuronal regeneration in vivo.     

Role of c-kit/Kit ligand signaling in regulating vasculogenesis

Mobilization into peripheral blood of bone marrow-derived cells including hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs), is regulated by chemokines/cytokines. These cells can contribute to the formation of new blood vessels (vasculogenesis) under pathological conditions including atherosclerosis, wound healing and tumor growth. We will review how these cells are mobilized into circulation, and supplied to the sites, where vessel formation is needed (i.e. ischemic tissue or tumor bed). We will give evidence that matrix metallo-proteinase-9 mediated Kit ligand (Stem cell factor) processing is essential for cell mobilization induced by chemo-/cytokines, like vascular endothelial growth factor (VEGF), Placental growth factor (PlGF), stromal cell derived factor-1 (SDF-1). These studies may provide the basis for the development of new therapeutic strategies for vascular diseases through targeting kit ligand mediated mobilization and homing of bone marrow-derived progenitor cells for cell therapy and cancer therapy.