Lineage- and developmental stage-specific mechanomodulation of induced pluripotent stem cell differentiation

• Published in: Stem cell research & therapy 2017-09, Vol.8 (1), p.216-216, Article 216
• Main Authors: Maldonado, Maricela, Luu, Rebeccah J, Ico, Gerardo, Ospina, Alex, Myung, Danielle, Shih, Hung Ping, Nam, Jin
• Format: Article
• Language: English
• Subjects: Biomedical materials; Cell Differentiation; Cell Line; Cell Lineage; Chondrocytes; Chondrogenesis; Collagen; Differentiation; Efficiency; Elastic Modulus; Embryos; Endoderm; Humans; Immunofluorescence; Induced pluripotent stem cells; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Inhibitory postsynaptic potentials; Mechanical properties; Mechanobiology; Microscopy; Morphology; Nanofibers - chemistry; Pancreas; Pluripotency; Polymerase chain reaction; Primary Cell Culture - methods; Properties; Protein expression; Short Report; Stem cell research; Stem cells; Substrate stiffness; Surface chemistry; Therapeutic applications; Tissue Scaffolds - chemistry
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-017-0667-2

To maximize the translational utility of human induced pluripotent stem cells (iPSCs), the ability to precisely modulate the differentiation of iPSCs to target phenotypes is critical. Although the effects of the physical cell niche on stem cell differentiation are well documented, current approaches to direct step-wise differentiation of iPSCs have been typically limited to the optimization of soluble factors. In this regard, we investigated how temporally varied substrate stiffness affects the step-wise differentiation of iPSCs towards various lineages/phenotypes. Electrospun nanofibrous substrates with different reduced Young's modulus were utilized to subject cells to different mechanical environments during the differentiation process towards representative phenotypes from each of three germ layer derivatives including motor neuron, pancreatic endoderm, and chondrocyte. Phenotype-specific markers of each lineage/stage were utilized to determine differentiation efficiency by reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence imaging for gene and protein expression analysis, respectively. The results presented in this proof-of-concept study are the first to systematically demonstrate the significant role of the temporally varied mechanical microenvironment on the differentiation of stem cells. Our results demonstrate that the process of differentiation from pluripotent cells to functional end-phenotypes is mechanoresponsive in a lineage- and differentiation stage-specific manner. Lineage/developmental stage-dependent optimization of electrospun substrate stiffness provides a unique opportunity to enhance differentiation efficiency of iPSCs for their facilitated therapeutic applications.