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 journalArticle

26 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 1

Fingerprint

Stem cells
MicroRNAs
Bone Marrow Cells
Nanoparticles
Bone
Induced Pluripotent Stem Cells
CD15 Antigens
Feeder Cells
Molecules
Macrophages
Fibroblasts
Embryonic Stem Cells
Polymers
Genes
Chemical activation
Proteins
Stem Cells
Bone Marrow
Messenger RNA
Acids

All Science Journal Classification (ASJC) codes

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

Cite this

Sohn, Young Doug ; Somasuntharam, Inthirai ; Che, Pao Lin ; Jayswal, Rishim ; Murthy, Niren ; Davis, Michael E. ; Yoon, Young sup. / Induction of pluripotency in bone marrow mononuclear cells via polyketal nanoparticle-mediated delivery of mature microRNAs. In: Biomaterials. 2013 ; Vol. 34, No. 17. pp. 4235-4241.
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Induction of pluripotency in bone marrow mononuclear cells via polyketal nanoparticle-mediated delivery of mature microRNAs. / Sohn, Young Doug; Somasuntharam, Inthirai; Che, Pao Lin; Jayswal, Rishim; Murthy, Niren; Davis, Michael E.; Yoon, Young sup.

In: Biomaterials, Vol. 34, No. 17, 01.06.2013, p. 4235-4241.

Research output: Contribution to journalArticle

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