Amniotic stromal stem cell-loaded hydrogel repairs cardiac tissue in infarcted rat hearts via paracrine mediators.

RT-PCR Wnt-signaling extracellular vesicles mass spectrometry mesenchymal stem cells myocardial infarction

Journal

Journal of tissue engineering and regenerative medicine
ISSN: 1932-7005
Titre abrégé: J Tissue Eng Regen Med
Pays: England
ID NLM: 101308490

Informations de publication

Date de publication:
02 2022
Historique:
revised: 18 09 2021
received: 28 12 2020
accepted: 19 10 2021
pubmed: 3 11 2021
medline: 5 4 2022
entrez: 2 11 2021
Statut: ppublish

Résumé

The use of stem cells to repair the heart after a myocardial infarction (MI) remains promising, yet clinical trials over the past 20 years suggest that cells fail to integrate into the native tissue, resulting in limited improvements in cardiac function. Here, we demonstrate the cardioprotective potential of a composite inserting human amniotic stromal mesenchymal stem cells (ASMCs) in a chitosan and hyaluronic acid (C/HA) based hydrogel in a rat MI model. Mechanical characterization of the C/HA platform indicated a swift elastic conversion at 40°C and a rapid sol-gel transition time at 37°C. Cell viability assay presented active and proliferating AMSCs in the C/HA. The ASMCs + C/HA injected composite significantly increased left ventricular ejection fraction, fractional shortening, and neovessel formation. The encapsulated AMSCs were abundantly detected in the infarcted myocardium 6 weeks post-administration and co-expressed cardiac proteins and notably proliferative markers. Proteomic profiling revealed that extracellular vesicles released from hypoxia preconditioned ASMCs contained proteins involved in cytoprotection, angiogenesis, cardiac differentiation and non-canonical Wnt-signaling. Independent activation of non-canonical Wnt-signaling pathways in ASMCs induced cardiogenesis. Despite a low injected cellular density at baseline, the encapsulated AMSCs were abundantly retained and increased cardiac function. Furthermore, the C/HA hydrogel provided an active milieu for the AMSCs to proliferate, co-express cardiac proteins, and induce new vessel formation. Hence, this novel composite of AMSCs + C/HA scaffold is a conceivable candidate that could restore cardiac function and reduce remodeling.

Identifiants

pubmed: 34726328
doi: 10.1002/term.3262
doi:

Substances chimiques

Hydrogels 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

110-127

Subventions

Organisme : CIHR
Pays : Canada
Organisme : Richard and Edith Strauss Foundation
Organisme : NSERC
Organisme : CIHR
Pays : Canada

Informations de copyright

© 2021 John Wiley & Sons Ltd.

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Auteurs

Kashif Khan (K)

Divisions of Cardiology and Cardiac Surgery, McGill University Health Centre, Montreal, Quebec, Canada.

Georges Makhoul (G)

Divisions of Cardiology and Cardiac Surgery, McGill University Health Centre, Montreal, Quebec, Canada.

Bin Yu (B)

Divisions of Cardiology and Cardiac Surgery, McGill University Health Centre, Montreal, Quebec, Canada.

Ghulam Jalani (G)

Department of Mining and Materials Engineering, McGill University, Montreal, Quebec, Canada.

Ida Derish (I)

Divisions of Cardiology and Cardiac Surgery, McGill University Health Centre, Montreal, Quebec, Canada.

Alissa K Rutman (AK)

Human Islet Transplant Laboratory, Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada.

Marta Cerruti (M)

Divisions of Cardiology and Cardiac Surgery, McGill University Health Centre, Montreal, Quebec, Canada.

Adel Schwertani (A)

Divisions of Cardiology and Cardiac Surgery, McGill University Health Centre, Montreal, Quebec, Canada.

Renzo Cecere (R)

Divisions of Cardiology and Cardiac Surgery, McGill University Health Centre, Montreal, Quebec, Canada.
The Royal Victoria Hospital Montreal, Montreal, Quebec, Canada.

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