Mesenchymal stem cells for pre-vascularization of engineered tissues
Mesenchymal stem cells for pre-vascularization of engineered tissues
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DOI：
10.15406/jsrt.2018.04.00112
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发表时间：
2018-04
期刊：
影响因子：
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通讯作者：
Dhavan Sharma;Juan Chica;F. Zhao
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文献类型：
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作者：
Dhavan Sharma;Juan Chica;F. Zhao
干细胞生物学和组织工程领域的最新进展使治疗各种疾病的方法发生了革命性的变化，特别是慢性伤口、骨骼疾病、心血管并发症和神经退行性疾病。为了设计合适的治疗方法，已经对不同类型的干细胞进行了研究。其中，涉及胚胎和诱导多能干细胞(IPSCs)的方法在伦理和社会上都存在争议。此外，由于这些干细胞类型的高度多能性，存在形成畸胎瘤的风险。1，2在过去的十年中，间充质干细胞(MSCs)由于其直接和侵入性较小的分离过程以及其多向分化的潜力而引起了人们的极大关注。MSCs可分化为多种细胞类型，包括成骨细胞、软骨细胞、脂肪细胞、平滑肌样细胞、内皮样细胞和心肌样细胞。此外，由于免疫缺陷，同种异体骨髓间充质干细胞发生免疫排斥的风险最小。它们还分泌各种营养因子，促进细胞存活和组织再生。3、4这些良好的能力使MSCs成为构建各种组织工程产品的潜在候选者。然而，厚度大于150μm的工程化组织需要一个功能强大的微血管网络来供应气体、营养物质和代谢副产品，并在植入后与宿主血管整合。5在生理性毛细血管结构中，内皮细胞包围着管腔。这些内皮细胞本身被周细胞包裹，从而稳定毛细血管结构。6大量研究证实，MSCs可以作为周细胞发挥作用。7，8因此，为了在组织支架中形成毛细血管网络，过去几年不同的研究小组研究了MSC-EC联合培养的结果。9-12与其他周细胞候选细胞相比，MSCs有望发挥双重作用：稳定工程微血管和在植入后执行干细胞功能。在这篇简短的综述中，我们讨论了成功的MSC-EC共培养以实现强大的血管网络的重要考虑因素。这些考虑因素包括适当的细胞来源、细胞接种顺序、最佳氧气水平、适当的细胞外基质(ECM)和组织支架功能(图1)。图1骨髓间充质干细胞-血管内皮细胞共培养发展预血运工程化组织的注意事项。(A)可从多种来源分离MSCs；(B)MSCs可在ECs形成的预先形成的血管网络上培养。相比之下，在MSC片上培养的ECs形成了更好的血管网络，(C)MSCs在低氧环境中保持干性并增加血管生成生长因子的分泌。然而，内皮细胞更喜欢常氧环境，以利于细胞的生存、增殖和血管网络的发展。(4)各种天然和合成材料支持MSC-EC共培养。脱细胞的ECM促进了强大的血管网络的发展。
Recent advances in the field of stem cell biology and tissue engineering have revolutionized therapeutic approaches to treat various diseases, especially chronic wounds, bone diseases, cardiovascular complications, and neurodegenerative diseases. Different stem cell types have been investigated for designing appropriate therapeutic treatments. Among them, approaches involving embryonic and induced pluripotent stem cells (iPSCs) are ethically and socially controversial. In addition, these stem cell types, due to their high pluripotency, contain risks of teratoma formation.1,2 In the past decade, mesenchymal stem cells (MSCs) have attracted considerable attention due to their straightforward and less invasive isolation procedure as well as their multi-differentiation potential. MSCs can differentiate into various cell types including osteoblasts, chondrocytes, adipocytes, smooth muscle like cells, endothelial like cells and cardiomyocyte like cells. Moreover, being immunoprivileged, allogenic MSCs encounter minimal risk of immune rejection. They also secrete various trophic factors, which can promote cell survival and tissue regeneration.3,4 These promising capabilities have made MSCs potential candidate for construction of various tissue-engineered products. Nevertheless, engineered tissues with a thickness larger than 150μm require a functional micro vascular network to supply gases, nutrients, metabolic byproducts, and integrate with host vasculature after implantation.5 In the physiological capillary structure, endothelial cells (ECs) surround the vessel lumen. These ECs are themselves wrapped by pericytes, which stabilize the capillary structure.6 Numerous studies have confirmed that MSCs can function as pericytes.7,8 Consequently, in order to develop a capillary network in tissue scaffolds various research groups over past several years have investigated the outcome of MSC-EC co-cultures.9‒12 Compared with other pericyte candidates, MSCs are expected to play dual roles: stabilizing engineered micro vessels and performing their stem cell functions after implantation. In this mini review, we discuss important considerations for successful MSC-EC co-cultures to achieve a robust vascular network. These considerations include an appropriate cell source, cell-seeding order, optimum oxygen (O2) levels, appropriate extracellular matrix (ECM) and tissue scaffold features (Figure 1). Figure 1 Considerations for MSC-EC co-culture for development of prevascularized engineered tissues. (A) Various sources from which MSCs can be isolated, (B) MSCs can be cultured on preformed vascular networks formed by ECs. In contrast, ECs cultured on MSC sheet forms better vascular networks, (C) MSCs maintain stemness and increase angiogenic growth factor secretion in a hypoxic environment. Whereas, ECs prefer normoxic environment for cell survival, proliferation and development of vascular networks, (D) Various natural and synthetic materials support MSC-EC co-culture. Decellularized ECM promotes development of robust vascular networks.