Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium

Anna Blocki, Sebastian Beyer, Jean Yves Dewavrin, Anna Goralczyk, Yingting Wang, Priscilla Peh, Michael Ng, Shehzahdi S. Moonshi, Susmitha Vuddagiri, Michael Raghunath, Eliana Cecilia Martinez Valencia, Kishore K. Bhakoo

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The limited efficacy of cardiac cell-based therapy is thought to be due to poor cell retention within the myocardium. Hence, there is an urgent need for biomaterials that aid in long-term cell retention. This study describes the development of injectable microcapsules for the delivery of mesenchymal stem cells (MSCs) into the infarcted cardiac wall. These microcapsules comprise of low concentrations of agarose supplemented with extracellular matrix (ECM) proteins collagen and fibrin. Dextran sulfate, a negatively charged polycarbohydrate, was added to mimic glycosaminoglycans in the ECM. Cell viability assays showed that a combination of all components is necessary to support long-term survival and proliferation of MSCs within microcapsules. Following intramyocardial transplantation, microcapsules degraded slowly invivo and did not induce a fibrotic foreign body response. Pre-labeling of encapsulated MSCs with iron oxide nanoparticles allowed continued cell-tracking by MRI over several weeks following transplantation into infarcted myocardium. In contrast, MSCs injected as cell suspension were only detectable for two days post transplantation by MRI. Histological analysis confirmed integration of transplanted cells at the infarct site. Therefore, microcapsules proved to be suitable for stem cell delivery into the infarcted myocardium and can overcome current limitations of poor cell retention in cardiac cell-based therapy.

Original languageEnglish (US)
Pages (from-to)12-24
Number of pages13
JournalBiomaterials
Volume53
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

Fingerprint

Stem cells
Mesenchymal Stromal Cells
Capsules
Cell Survival
Myocardium
Cell Proliferation
Transplantation
Cell- and Tissue-Based Therapy
Magnetic resonance imaging
Cell Tracking
Dextran Sulfate
Dextran
Extracellular Matrix Proteins
Biocompatible Materials
Foreign Bodies
Glycosaminoglycans
Fibrin
Iron oxides
Collagen
Biomaterials

Keywords

  • Biocompatibility
  • Cell encapsulation
  • Cell therapy
  • Foreign body response
  • Invivo cell tracking
  • Myocardial infarction

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium. / Blocki, Anna; Beyer, Sebastian; Dewavrin, Jean Yves; Goralczyk, Anna; Wang, Yingting; Peh, Priscilla; Ng, Michael; Moonshi, Shehzahdi S.; Vuddagiri, Susmitha; Raghunath, Michael; Martinez Valencia, Eliana Cecilia; Bhakoo, Kishore K.

In: Biomaterials, Vol. 53, 01.06.2015, p. 12-24.

Research output: Contribution to journalArticle

Blocki, A, Beyer, S, Dewavrin, JY, Goralczyk, A, Wang, Y, Peh, P, Ng, M, Moonshi, SS, Vuddagiri, S, Raghunath, M, Martinez Valencia, EC & Bhakoo, KK 2015, 'Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium', Biomaterials, vol. 53, pp. 12-24. https://doi.org/10.1016/j.biomaterials.2015.02.075
Blocki, Anna ; Beyer, Sebastian ; Dewavrin, Jean Yves ; Goralczyk, Anna ; Wang, Yingting ; Peh, Priscilla ; Ng, Michael ; Moonshi, Shehzahdi S. ; Vuddagiri, Susmitha ; Raghunath, Michael ; Martinez Valencia, Eliana Cecilia ; Bhakoo, Kishore K. / Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium. In: Biomaterials. 2015 ; Vol. 53. pp. 12-24.
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