Two Stem Cell Populations Including VSELs and CSCs Detected in the Pericardium of Adult Mouse Heart,Stem Cell Reviews and Reports

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Two Stem Cell Populations Including VSELs and CSCs Detected in the Pericardium of Adult Mouse Heart
Stem Cell Reviews and Reports ( IF 4.5 ) Pub Date : 2021-01-25 , DOI: 10.1007/s12015-021-10119-9
Deepa Bhartiya ₁ , Yash Flora ₁ , Diksha Sharma ₁ , Subhan Ali Mohammad ₁

Affiliation

Adult mammalian heart is considered to be one of the least regenerative organs as it is not able to initiate endogenous regeneration in response to injury unlike in lower vertebrates and neonatal mammals. Evidence is now accumulating to suggest normal renewal and replacement of cardiomyocytes occurs even in middle-aged and old individuals. But underlying mechanisms leading to this are not yet clear. Do tissue-resident stem cells exist or somatic cells dedifferentiate leading to regeneration? Lot of attention is currently being focused on epicardium as it is involved in cardiac development, lodges multipotent progenitors and is a source of growth factors. Present study was undertaken to study the presence of stem cells in the pericardium. Intact adult mouse heart was subjected to partial enzymatic digestion to collect the pericardial cells dislodged from the surface. Pericardial cells suspension was processed to enrich the stem cells using our recently published protocol. Two populations of stem cells were successfully enriched from the pericardium of adult mouse heart along with distinct ‘cardiospheres’ with cytoplasmic continuity (formed by rapid proliferation and incomplete cytokinesis). These included very small embryonic-like stem cells (VSELs) and slightly bigger ‘progenitors’ cardiac stem cells (CSCs). Expression of pluripotent (Oct-4A, Sox-2, Nanog), primordial germ cells (Stella, Fragilis) and CSCs (Oct-4, Sca-1) specific transcripts was studied by RT-PCR. Stem cells expressed OCT-4, NANOG, SSEA-1, SCA-1 and c-KIT. c-KIT was expressed by cells of different sizes but only smaller CD45⁻c-KIT⁺ VSELs possess regenerative potential. Inadvertent loss of stem cells while processing for different experiments has led to misperceptions & controversies existing in the field of cardiac stem cells and requires urgent rectification. VSELs/CSCs have the potential to regenerate damaged cardiac tissue in the presence of paracrine support provided by the mesenchymal stromal cells.

Graphical Abstract

中文翻译：

在成年小鼠心脏的心包中检测到两种干细胞群，包括 VSEL 和 CSC

成年哺乳动物心脏被认为是再生能力最低的器官之一，因为与低等脊椎动物和新生哺乳动物不同，它不能启动内源性再生以响应损伤。现在越来越多的证据表明，即使在中年和老年人中，心肌细胞也会正常更新和更换。但导致这种情况的潜在机制尚不清楚。是否存在组织驻留干细胞或体细胞去分化导致再生？目前很多注意力都集中在心外膜上，因为它参与心脏发育，容纳多能祖细胞并且是生长因子的来源。本研究旨在研究心包中干细胞的存在。对完整的成年小鼠心脏进行部分酶消化以收集从表面脱落的心包细胞。使用我们最近发布的协议处理心包细胞悬浮液以丰富干细胞。成功地从成年小鼠心脏的心包中富集了两个干细胞群，以及具有细胞质连续性（由快速增殖和不完全胞质分裂形成）的不同“心脏球”。这些包括非常小的胚胎样干细胞 (VSEL) 和稍大的“祖细胞”心脏干细胞 (CSC)。多能表达 ( 成功地从成年小鼠心脏的心包中富集了两个干细胞群，以及具有细胞质连续性（由快速增殖和不完全胞质分裂形成）的不同“心脏球”。这些包括非常小的胚胎样干细胞 (VSEL) 和稍大的“祖细胞”心脏干细胞 (CSC)。多能表达 ( 成功地从成年小鼠心脏的心包中富集了两个干细胞群，以及具有细胞质连续性（由快速增殖和不完全胞质分裂形成）的不同“心脏球”。这些包括非常小的胚胎样干细胞 (VSEL) 和稍大的“祖细胞”心脏干细胞 (CSC)。多能表达 (通过 RT-PCR 研究Oct-4A、Sox-2、Nanog )、原始生殖细胞 ( Stella, Fragilis ) 和 CSC ( Oct-4, Sca-1) 特异性转录物。干细胞表达 OCT-4、NANOG、SSEA-1、SCA-1 和 c-KIT。c-KIT 由不同大小的细胞表达，但只有较小的 CD45 ^- c-KIT ⁺ VSELs 具有再生潜力。在处理不同实验时无意中丢失了干细胞，导致心脏干细胞领域存在误解和争议，需要紧急纠正。在间充质基质细胞提供旁分泌支持的情况下，VSELs/CSCs 具有再生受损心脏组织的潜力。

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更新日期：2021-01-25

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