Induction of pluripotency in bone marrow mononuclear cells via polyketal nanoparticle-mediated delivery of mature microRNAs

Young Doug Sohn, Inthirai Somasuntharam, Pao Lin Che, Rishim Jayswal, Niren Murthy, Michael E. Davis, Young sup Yoon

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Since the successful generation of induced pluripotent stem cells (iPSC) from adult somatic cells using integrating-viral methods, various methods have been tried for iPSC generation using non-viral and non-integrating technique for clinical applications. Recently, various non-viral approaches such as protein, mRNA, microRNA, and small molecule transduction were developed to avoid genomic integration and generate stem cell-like cells from mouse and human fibroblasts. Despite these successes, there has been no successful generation of iPSC from bone marrow (BM)-derived hematopoietic cells derived using non-viral methods to date. Previous reports demonstrate the ability of polymeric micro and nanoparticles made from polyketals to deliver various molecules to macrophages. MicroRNA-loaded nanoparticles were created using the polyketal polymer PK3 (PK3-miR) and delivered to somatic cells for 6 days, resulting in the formation of colonies. Isolated cells from these colonies were assayed and substantial induction of the pluripotency markers Oct4, Sox2, and Nanog were detected. Moreover, colonies transferred to feeder layers also stained positive for pluripotency markers including SSEA-1. Here, we demonstrate successful activation of pluripotency-associated genes in mouse BM-mononuclear cells using embryonic stem cell (ESC)-specific microRNAs encapsulated in the acid sensitive polyketal PK3. These reprogramming results demonstrate that a polyketal-microRNA delivery vehicle can be used to generate various reprogrammed cells without permanent genetic manipulation in an efficient manner.

Original languageEnglish
Pages (from-to)4235-4241
Number of pages7
JournalBiomaterials
Volume34
Issue number17
DOIs
Publication statusPublished - 2013 Jun

Bibliographical note

Funding Information:
This work has been funded in whole or in part with grants from National Institutes of Health , Department of Health and Human Services , under Contract No. HHSN268201000043C to Y-s Y and MED; HL090601 to MED, DP3DK094346 to Y-s Y, UL1 RR025008 from the Clinical and Translational Science Award Program, NCRR to Y-s Y, and from NSF-EBICS (Emergent Behaviors of Integrated Cellular Systems) grant, CBET-0939511 to Y-s Y.

All Science Journal Classification (ASJC) codes

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

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