Stem cell therapies for heart disease: why do we need bioengineers?
Stem cell therapies for heart disease: why do we need bioengineers?
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心脏病的干细胞疗法：为什么我们需要生物工程师？
DOI：
10.1109/memb.2007.384101
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Bursac,Nenad
中科院分区：
文献类型：
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作者：
Bursac,Nenad
心脏通过细胞增殖或干细胞募集的有限再生潜力不足以弥补急性心肌梗死后的组织损失。因此，对存活心肌增加的负荷常常导致心力衰竭。每年大约有86.5万美国人患有心肌梗死，近490万人患有心力衰竭，这表明迫切需要新的、更有效的治疗方法。十多年前，外源细胞移植到心脏中被提出作为一种方法来增强这些疾病中受损的心脏功能[2]，b[4]。目前，利用干细胞重建受损心脏已成为心脏研究的主流实验概念。此外，心脏病的严重程度和心力衰竭患者数量的增加促使了在临床实践中实施干细胞治疗的尝试。虽然参与临床研究的患者数量在不断增加，但我们对移植细胞在心脏修复中的潜在作用的了解仍然有限。要回答的主要问题是：哪种心脏病以及何时应该治疗？哪种细胞类型或细胞类型的组合将是最有益的，安全的，并产生持久的心脏功能改善？这些细胞应该如何运送？移植细胞影响心脏功能的机制是什么？如何利用这些知识来促进组织修复和再生新方法的发展？尽管存在许多未优化的变量，但使用自体骨骼肌母细胞[5]和骨髓源性干细胞[6]的初步临床尝试显示出轻微但显著的心脏功能改善，这很可能是由于植入细胞的旁分泌作用和梗死区域血管化的增加。然而，双盲随机安慰剂对照试验的最新结果却不那么令人鼓舞。目前已经认识到一些主要的障碍，包括植入细胞的保留率和存活率低，以及宿主心脏组织内递送细胞的心源性分化和功能整合有限。特别是，不理想的细胞递送到心脏的方法已被证明会导致注射部位不受控制的细胞损失（甚至90%）和所得到的移植物大小[2]的巨大变化。将生物活性水凝胶与注射的细胞混合，然后进行细胞/水凝胶原位聚合，可以最大限度地减少细胞损失。然而，即使大量细胞被有效地保留在注射部位，它们在恶劣的梗死环境中的存活也不能得到保证，更高的细胞密度可能导致更高的细胞死亡率。目前⁓90%成功递送的细胞在注射[2]后的第一周内死亡。为了克服这一问题，研究人员正在探索在细胞植入[13]之前进行热休克治疗，以及外源性递送抗凋亡和血管生成因子[14]-[16]或其在植入细胞[17]，[18]中的过表达。
The limited regenerative potential of the heart via cell proliferation or stem cell recruitment is insufficient to compensate for tissue loss after an acute myocardial infarction [1],[2]. Consequently, the increased workload placed on the surviving myocardium often leads to heart failure. Approximately 865,000 Americans per year suffer a myocardial infarction and nearly 4.9 million are afflicted with heart failure, demonstrating the vital need for new and more efficient therapies [3]. More than a decade ago, the transplantation of exogenous cells into the heart had been proposed as a method to augment compromised heart function in these diseases [2],[4]. Nowadays, the use of stem cells to rebuild a damaged heart has become a mainstream experimental concept in cardiac research. Moreover, the severity of heart disease and the increasing numbers of heart failure patients have prompted attempts to implement the stem cell therapies in clinical practice. While the number of enrolled patients in clinical studies is growing, our understanding of the potential role of transplanted cells in cardiac repair is limited. The main questions to be answered are: Which heart disease and when should it be treated? Which cell type or combination of cell types will be the most beneficial, safe, and yield longlasting improvement of heart function? How should these cells be delivered? What are the mechanisms by which transplanted cells affect heart function, and how can this knowledge be used to promote the development of new methods for tissue repair and regeneration?Despite a number of unoptimized variables, initial clinical attempts using autologous skeletal myoblasts [5] and bone marrow-derived stem cells [6] have demonstrated slight but significant improvements in heart function, most likely due to the paracrine action of implanted cells and increased vascularization of the infarct area. However, the latest results of double-blind randomized placebo-controlled trials have been less encouraging [7]–[10]. Some of the main hurdles have been recognized, including low retention and survival of implanted cells, as well as limited cardiogenic differentiation and functional integration of delivered cells within the host heart tissue. In particular, suboptimal methods for cell delivery into the heart have been shown to result in uncontrolled cell loss (even> 90%) from the injection site and large variability of the resulting graft size [2]. The mixing of bioactive hydrogels with injected cells and subsequent cell/hydrogel polymerization in situ can be used to minimize cell loss [11],[12]. However, even if a high number of cells are efficiently retained at the injection site, their survival within the harsh infarct environment is not guaranteed and higher cell densities may lead to even higher cell mortality. Currently⁓ 90% of successfully delivered cells are shown to die within the first week after injection [2]. Heat shock treatment prior to cell implantation [13] as well as exogenous delivery of anti-apoptotic and angiogenic factors [14]–[16] or their overexpression in implanted cells [17],[18] are being explored in an attempt to overcome this problem.
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DOI：
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发表时间：
--
期刊：
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影响因子：
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作者：
通讯作者：
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影响因子：
6.1
作者：
Chen S;Zhu P;Guo HM;Solis RS;Wang Y;Ma Y;Wang J;Gao J;Chen JM;Ge Y;Zhuang J;Li J
通讯作者：
Li J
影响因子：
20.1
作者：
Feaster TK;Cadar AG;Wang L;Williams CH;Chun YW;Hempel JE;Bloodworth N;Merryman WD;Lim CC;Wu JC;Knollmann BC;Hong CC
通讯作者：
Hong CC
影响因子：
39.3
作者：
Haddad, Saba;Wang, Yong;Kempf, Tibor
通讯作者：
Kempf, Tibor
影响因子：
8.8
作者：
Rensvold JW;Ong SE;Jeevananthan A;Carr SA;Mootha VK;Pagliarini DJ
通讯作者：
Pagliarini DJ