Multi-Investigator Letter on Reproducibility of Neonatal Heart Regeneration following Apical Resection

Sadek, Hesham A.; Martin, James F.; Takeuchi, Jun; Leor, Jonathan; Nie, Yu; Giacca, Mauro; Lee, Richard T.

doi:10.1016/j.stemcr.2014.06.009

Cited by 50 publications

(42 citation statements)

References 7 publications

(9 reference statements)

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“…Interestingly, a recent report has raised questions and discussion regarding the regenerative capacity of neonatal mouse hearts after ventricular resection (Andersen et al, 2014a; Andersen et al, 2014b; Sadek et al, 2014). Based on our results, the discrepancy might be partially explained by differences in the severities of the injuries created.…”

Section: Discussionmentioning

confidence: 99%

Differential regenerative capacity of neonatal mouse hearts after cryoinjury

Darehzereshki

Rubin

Gamba

et al. 2015

Developmental Biology

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Neonatal mouse hearts fully regenerate after ventricular resection similar to adult zebrafish. We established cryoinjury models to determine if different types and varying degrees of severity in cardiac injuries trigger different responses in neonatal mouse hearts. In contrast to ventricular resection, neonatal mouse hearts fail to regenerate and show severe impairment of cardiac function post transmural cryoinjury. However, neonatal hearts fully recover after non-transmural cryoinjury. Interestingly, cardiomyocyte proliferation does not significantly increase in neonatal mouse hearts after cryoinjuries. Epicardial activation and new coronary vessel formation occur after cryoinjury. The profibrotic marker PAI-1 is highly expressed after transmural but not non-transmural cryoinjuries, which may contribute to the differential scarring. Our results suggest that regenerative medicine strategies for heart injuries should vary depending on the nature of the injury.

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Section: Discussionmentioning

confidence: 99%

Differential regenerative capacity of neonatal mouse hearts after cryoinjury

Darehzereshki

Rubin

Gamba

et al. 2015

Developmental Biology

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“…within trabecular or cortical bone) could have an additional impact on their in vivo composition [50–52]. To assess potential differences in MSCs selected from BM aspirates, FHs and RIA, we investigated the relative expression of two additional markers that have been suggested to offer highly specific selection for MSCs in BM, MSCA-1 and SUSD2 [38,39].…”

Section: Discussionmentioning

confidence: 99%

Examining the Feasibility of Clinical Grade CD271+ Enrichment of Mesenchymal Stromal Cells for Bone Regeneration

et al. 2015

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IntroductionCurrent clinical trials utilize mesenchymal stromal cells (MSCs) expanded in culture, however these interventions carry considerable costs and concerns pertaining to culture-induced losses of potency. This study assessed the feasibility of new clinical-grade technology to obtain uncultured MSC isolates from three human intra-osseous tissue sources based on immunomagnetic selection for CD271-positive cells.Materials and MethodsMSCs were isolated from bone marrow (BM) aspirates or surgical waste materials; enzymatically digested femoral heads (FHs) and reamer irrigator aspirator (RIA) waste fluids. Flow cytometry for the CD45−/lowCD73+CD271+ phenotype was used to evaluate uncultured MSCs before and after selection, and to measure MSC enrichment in parallel to colony forming-unit fibroblast assay. Trilineage differentiation assays and quantitative polymerase chain-reaction for key transcripts involved in bone regeneration was used to assess the functional utility of isolated cells for bone repair.ResultsUncultured CD45−/lowCD271+ MSCs uniformly expressed CD73, CD90 and CD105 but showed variable expression of MSCA-1 and SUSD2 (BM>RIA>FH). MSCs were enriched over 150-fold from BM aspirates and RIA fluids, whereas the highest MSC purities were obtained from FH digests. Enriched fractions expressed increased levels of BMP-2, COL1A2, VEGFC, SPARC and CXCL12 transcripts (BM>RIA>FH), with the highest up-regulation detected for CXCL12 in BM (>1300-fold). Following culture expansion, CD271-selected MSCS were tri-potential and phenotypically identical to plastic adherence-selected MSCs.DiscussionA CD271-based GMP-compliant immunomagnetic selection resulted in a substantial increase in MSC purity and elevated expression of transcripts involved in bone formation, vascularisation and chemo-attraction. Although this technology, particularly from RIA fluids, can be immediately applied by orthopaedic surgeons as autologous therapy, further improvements in MSC purities and pre-clinical testing of product safety would be required to develop this process for allogeneic applications.

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“…In contrast, differences in the capacity for complete regeneration of neonatal mouse hearts after apical resection have been reported by different laboratories [82–87]. Andersen et al showed that apically resected myocardium is not regenerated, despite claims of similar amounts of tissue (or less) removed (~8.5% versus ~15% in Porrello et al).…”

Section: Regenerative Responses To Different Severities Of Injuriesmentioning

confidence: 99%

Recent advancements in understanding endogenous heart regeneration—insights from adult zebrafish and neonatal mice

Rubin

Harrison

Krainock

et al. 2016

Seminars in Cell & Developmental Biology

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Enhancing the endogenous regenerative capacity of the mammalian heart is a promising strategy that can lead to potential treatment of injured cardiac tissues. Studies on heart regeneration in zebrafish and neonatal mice have shown that cardiomyocyte proliferation is essential for replenishing myocardium. We will review recent advancements that have demonstrated the importance of Neuregulin 1/ErbB2 and innervation in regulating cardiomyocyte proliferation using both adult zebrafish and neonatal mouse heart regeneration models. Emerging findings suggest that different populations of macrophages and inflammation might contribute to regenerative versus fibrotic responses. Finally, we will discuss variation in the severity of the cardiac injury and size of the wound, which may explain the range of outcomes observed in different injury models.

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Multi-Investigator Letter on Reproducibility of Neonatal Heart Regeneration following Apical Resection

Cited by 50 publications

References 7 publications

Differential regenerative capacity of neonatal mouse hearts after cryoinjury

Differential regenerative capacity of neonatal mouse hearts after cryoinjury

Examining the Feasibility of Clinical Grade CD271+ Enrichment of Mesenchymal Stromal Cells for Bone Regeneration

Recent advancements in understanding endogenous heart regeneration—insights from adult zebrafish and neonatal mice

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