Induced cardiac progenitor cells repopulate decellularized mouse heart scaffolds and differentiate to generate cardiac tissue.
Induced cardiac progenitor cells repopulate decellularized mouse heart scaffolds and differentiate to generate cardiac tissue.
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DOI：
10.1016/j.bbamcr.2019.118559
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发表时间：
2020-03
期刊：
影响因子：
--
通讯作者：
Kamp TJ
中科院分区：
文献类型：
--
作者：
Alexanian RA;Mahapatra K;Lang D;Vaidyanathan R;Markandeya YS;Gill RK;Zhai AJ;Dhillon A;Lea MR;Abozeid S;Schmuck EG;Raval AN;Eckhardt LL;Glukhov AV;Lalit PA;Kamp TJ
天然心肌损伤后再生潜力有限。除了研究应用之外，谱系重编程的进展还为再生医学提供了有前途的细胞来源。最近，我们已经表明，成年小鼠成纤维细胞可以重编程为可扩展的，多能的，诱导的心脏祖细胞（iCPC），通过采用强制表达的五个心脏因子沿着激活经典Wnt和JAK/STAT信号。在这里，我们的目标是通过强调其安全性，易获取性和三维心脏细胞外基质支架内的功能性来进一步表征iCPC。具体而言，iCPC在注射到免疫缺陷小鼠中时，与胚胎干细胞相比不会形成畸胎瘤。在野生型小鼠成纤维细胞中实现iCPC重编程，而不需要心脏特异性报告基因，仅利用形态学变化来鉴定、克隆分离和扩增iCPC，从而增加了该技术的通用性。iCPC还显示出重新填充脱细胞的天然心脏支架并分化成含有心肌细胞、平滑肌和内皮细胞的有组织结构的能力。再细胞化支架的光学映射显示了场刺激的钙瞬变，其跨越重构组织的岛传播，并且双极局部刺激证明了支架内的细胞-细胞偶联。总的来说，iCPC为各种应用提供了容易获得的、可扩展的、安全的和功能性的细胞来源，包括药物发现、疾病建模和再生治疗。
Native myocardium has limited regenerative potential post injury. Advances in lineage reprogramming have provided promising cellular sources for regenerative medicine in addition to research applications. Recently we have shown that adult mouse fibroblasts can be reprogrammed to expandable, multipotent, induced cardiac progenitor cells (iCPCs) by employing forced expression of five cardiac factors along with activation of canonical Wnt and JAK/STAT signaling. Here we aim to further characterize iCPCs by highlighting their safety, ease of attainability, and functionality within a three-dimensional cardiac extracellular matrix scaffold. Specifically, iCPCs did not form teratomas in contrast to embryonic stem cells when injected into immunodeficient mice. iCPC reprogramming was achieved in wild type mouse fibroblasts without requiring a cardiac-specific reporter, solely utilizing morphological changes to identify, clonally isolate, and expand iCPCs, thus increasing the versatility of this technology. iCPCs also show the ability to repopulate decellularized native heart scaffolds and differentiated into organized structures containing cardiomyocytes, smooth muscle, and endothelial cells. Optical mapping of recellularized scaffolds shows field-stimulated calcium transients that propagate across islands of reconstituted tissue and bipolar local stimulation demonstrates cell-cell coupling within scaffolds. Overall, iCPCs provide a readily attainable, scalable, safe, and functional cell source for a variety of application including drug discovery, disease modeling, and regenerative therapy.
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