Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, TN, India.
Stem Cell Rev Rep. 2013 Apr;9(2):158-71. doi: 10.1007/s12015-013-9427-6.
Cellular therapy using stem cells for cardiac diseases has recently gained much interest in the scientific community due to its potential in regenerating damaged and even dead tissue and thereby restoring the organ function. Stem cells from various sources and origin are being currently used for regeneration studies directly or along with differentiation inducing agents. Long term survival and minimal side effects can be attained by using autologous cells and reduced use of inducing agents. Cardiomyogenic differentiation of adult derived stem cells has been previously reported using various inducing agents but the use of a potentially harmful DNA demethylating agent 5-azacytidine (5-azaC) has been found to be critical in almost all studies. Alternate inducing factors and conditions/stimulant like physical condition including electrical stimulation, chemical inducers and biological agents have been attempted by numerous groups to induce cardiac differentiation. Biomaterials were initially used as artificial scaffold in in vitro studies and later as a delivery vehicle. Natural ECM is the ideal biological scaffold since it contains all the components of the tissue from which it was derived except for the living cells. Constructive remodeling can be performed using such natural ECM scaffolds and stem cells since, the cells can be delivered to the site of infraction and once delivered the cells adhere and are not "lost". Due to the niche like conditions of ECM, stem cells tend to differentiate into tissue specific cells and attain several characteristics similar to that of functional cells even in absence of any directed differentiation using external inducers. The development of niche mimicking biomaterials and hybrid biomaterial can further advance directed differentiation without specific induction. The mechanical and electrical integration of these materials to the functional tissue is a problem to be addressed. The search for the perfect extracellular matrix for therapeutic applications including engineering cardiac tissue structures for post ischemic cardiac tissue regeneration continues.
利用干细胞进行心脏疾病的细胞治疗最近在科学界引起了广泛关注，因为它有可能再生受损甚至死亡的组织，从而恢复器官功能。目前，各种来源和起源的干细胞正被用于直接或与诱导分化剂一起进行再生研究。通过使用自体细胞和减少诱导剂的使用，可以实现长期存活和最小的副作用。已经有研究报道，利用各种诱导剂可以使成体来源的干细胞向心肌细胞分化，但使用潜在有害的 DNA 去甲基化剂 5-氮杂胞苷（5-azaC）在几乎所有研究中都是至关重要的。许多研究小组尝试使用替代诱导因子和条件/刺激物，如物理条件（包括电刺激）、化学诱导剂和生物制剂，来诱导心脏分化。生物材料最初被用作体外研究中的人工支架，后来被用作递送载体。天然细胞外基质（ECM）是理想的生物支架，因为它包含了组织的所有成分，除了活细胞。可以使用这种天然 ECM 支架和干细胞进行建设性重塑，因为可以将细胞递送到损伤部位，一旦递送，细胞就会附着，而不会“丢失”。由于 ECM 具有类似小生境的条件，干细胞倾向于分化为组织特异性细胞，并获得与功能性细胞相似的几个特征，即使在没有任何外部诱导剂的定向分化的情况下也是如此。模仿小生境的生物材料和杂交生物材料的发展可以进一步推进无需特定诱导的定向分化。这些材料与功能性组织的机械和电整合是一个需要解决的问题。人们一直在寻找用于治疗应用的理想细胞外基质，包括用于缺血后心脏组织再生的工程心脏组织结构。
