Preprint Article Version 1 This version is not peer-reviewed

Growth Factor-free Chondrogenic Differentiation from Induced Pluripotent Stem Cells using Minicircle Vectors

Version 1 : Received: 1 April 2018 / Approved: 2 April 2018 / Online: 2 April 2018 (09:59:50 CEST)

How to cite: Rim, Y.A.; Nam, Y.; Ju, J.H. Growth Factor-free Chondrogenic Differentiation from Induced Pluripotent Stem Cells using Minicircle Vectors. Preprints 2018, 2018040017 (doi: 10.20944/preprints201804.0017.v1). Rim, Y.A.; Nam, Y.; Ju, J.H. Growth Factor-free Chondrogenic Differentiation from Induced Pluripotent Stem Cells using Minicircle Vectors. Preprints 2018, 2018040017 (doi: 10.20944/preprints201804.0017.v1).

Abstract

The human degenerative cartilage has low regenerative potential. Chondrocyte transplantation offers a promising strategy for cartilage treatment and regeneration. Currently chondrogenesis using human pluripotent stem cells are accomplished using human recombinant growth factors. Here, we differentiated human induced pluripotent stem cells (hiPSCs) into chondrocytes and cartilage pellet using minicircle vectors. Minicircles are used as a non-viral gene delivery system for gene therapy in various diseases. Non-viral gene delivery can produce growth factors without integrating into the host genome. Minicircle vectors containing bone morphogenetic protein 2 (BMP2) and transforming growth factor, beta 3 (TGFβ3) were successfully generated and delivered to hiPSC-derived outgrowth (OG) cells. Cell pellets generated using minicircle-transfected OG cells successfully differentiated into chondrogenic lineage. Chondrogenic pellets transfected with growth factor-encoding minicircles effectively recovered osteochondral defect in rat models. Taken together, this work shows the potential application of minicircles in cartilage regeneration using hiPSCs.

Subject Areas

minicircle; induced pluripotent stem cells; chondrogenesis; chondrocyte; bone morphogenetic proteins; transforming growth factors

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