# Study the mechanisms of interaction between hiPSC-derived endothelial (ECs) and skeletal myogenic progenitor cells (MPCs) in vitro and in vivo > **NIH NIH R21** · UNIVERSITY OF HOUSTON · 2024 · $177,872 ## Abstract Project Summary/ Abstract Human induced pluripotent stem cells (hiPSCs) are among the top candidates for cell therapy due to their pluripotency and isogenic source. In case of skeletal muscle disorders, stem cell-based therapies can replace defective or damaged muscle tissue with healthy muscle stem cells and progenitors. Therefore, hiPSCs have been the focus of recent research for derivation of skeletal muscle progenitor cells (MPCs). However, cell therapies are generally limited by poor cell survival due to lack of oxygen, nutrients and local trophic factors. Meanwhile, endothelial cells (ECs) have a key role in regulation of muscle stem cells through secretion of trophic factors controlling their activation, function and maturation. In addition, ECs directly contribute in angiogenesis and formation of new vessels, improving local circulation. Indeed, coupled activation of MPCs and ECs supports optimal muscle regeneration and plasticity after injuries or increased physiological demand. Therefore, ECs can be considered as a potential adjunctive cell therapy to improve MPC survival and engraftment outcome in vivo. Although the interaction between ECs and MPCs have been studied using primary cell lines and mouse models, their possible cross-talk, underlying molecular mechanisms and their combined in vivo engraftment efficiency has not been evaluated in a hiPSC-derived model system. Therefore, current application aims to: A) study the effect of hiPSC-ECs on in vitro activity and function of their myogenic counterparts (hiPSC-MPCs) and to identify and validate underlying mechanisms, and B) to evaluate the therapeutic efficiency of a combined hiPSC-EC+ MPC therapy in dystrophic or injury mouse models. In Aim1, hiPSC-ECs and MPCs will be grown using a transwell co-culture system to allow paracrine interaction of the cells. The paracrine effect of ECs on MPCs will be evaluated on cell proliferation, migration and differentiation using gene expression, transwell migration assay and immunostaining methods. In addition, time-course RNA-Seq and secretome proteomics will be performed to identify differentially expressed genes and proteins, such as ligands and receptor pairs, growth factors and pathways. Top candidates will be validated by proteomics and over-expression/inhibition studies to validate their role in the predicted cellular function. In Aim2, hiPSC-ECs and MPCs will be injected into muscle of dystrophic or injury mouse models using different cell ratios and their in vivo survival and engraftment will be evaluated by live cell bioluminescence, as well as histologic evaluation for donor cell engraftment into myofibers, muscle stem cell and vessel compartment. Data will be quantified for engraftment and vascularization among different experimental conditions to determine the efficiency and appropriate cell ratio of combined hiPSC-EC + MPC therapy in the studied models. Completion of these studies will elucidate the role and underlying mechanisms of... ## Key facts - **NIH application ID:** 10797762 - **Project number:** 1R21AR082319-01A1 - **Recipient organization:** UNIVERSITY OF HOUSTON - **Principal Investigator:** Radbod Darabi - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $177,872 - **Award type:** 1 - **Project period:** 2024-09-01 → 2026-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10797762 ## Citation > US National Institutes of Health, RePORTER application 10797762, Study the mechanisms of interaction between hiPSC-derived endothelial (ECs) and skeletal myogenic progenitor cells (MPCs) in vitro and in vivo (1R21AR082319-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10797762. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*