Engineering patient-specific valves using stem cells generated from skin biopsy specimens

David L. Simpson, Brody Wehman, Yekaterina Galat, Sudhish Sharma, Rachana Mishra, Vasiliy Galat, Sunjay Kaushal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background. Pediatric patients requiring valve replacement will likely require reoperations due to a progressive deterioration of valve durability and limited repair and growth potential. To address these concerns, we sought to generate a biologically active pulmonary valve using patient-specific valvular cells and decellularized human pulmonary valves. Methods. We generated induced pluripotent stem cells (iPSCs) by reprogramming skin fibroblast cells. We then differentiated iPSCs to mesenchymal stem cells (iPCSs-MSCs) using culture conditions that favored an epithelial-to-mesenchymal transition. Next, decellularized human pulmonary heart valves were seeded with iPCS-MSCs using a combination of static and dynamic culture conditions and cultured up to 30 days. Results. The iPSCs-MSCs displayed cluster of differentiation CD105 and CD90 expression exceeding 90% after four passages and could differentiate into osteocytes, chondrocytes, and adipocytes (n = 4). Consistent with an MSC phenotype, iPSCs-MSCs lacked expression of CD45 and CD34. Compared with bone marrow MSCs, iPSCs-MSC proliferated more readily by twofold but maintained a gene expression profile exceeding 80% identical to bone marrow MSCs. In repopulated pulmonary valves compared with decellularized pulmonary valves, immunohistochemistry demonstrated increased cellularity, α-smooth muscle actin expression, and increased presence of extracellular matrix components, such as proteoglycans and glycosaminoglycans, suggesting sustained cell function and maturation. Conclusions. Our results demonstrate the feasibility of constructing a biologically active human pulmonary valve using a sustainable and proliferative cell source. The bioactive pulmonary valve is expected to have advantages over existing valvular replacements, which will require further validation.

Original languageEnglish (US)
Pages (from-to)947-954
Number of pages8
JournalAnnals of Thoracic Surgery
Volume98
Issue number3
DOIs
StatePublished - Sep 2014

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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