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University of South Florida

Wanling Xuan

Principal Investigator (NIH-funded) · PHARMACOLOGY · USF

Affiliated program: Neuroscience PhD

This profile was assembled automatically from NIH RePORTER award records. Department and program affiliations are inferred and may be out of date — confirm on the university website.

Funding summary

Active NIH grants
4
Total NIH funding
$1.2M
Award records
4

Research topics

Matched from this investigator's NIH project titles and abstracts.

Active NIH awards

  • hiPS cells derived skeletal muscle progenitors and their extracellular vesicles for treatment of sarcopenia

    5R01AG070145-05

    NIA · FY 2025 · $301K

    PROJECT SUMMARY Aging of skeletal muscle results in sarcopenia. It is believed that sarcopenia is in part due to a decreased capacity of stem cells, namely satellite cells, to repair the skeletal muscle after injury. Satellite cells are the major source of myogenic progenitors for adult muscle homeostasis and repair. A potential alternative for dysfunctional satellite cells is induced pluripotent stem cells (iPSC) which have the capacity to differentiate into skeletal muscle myocytes and blood vessels. Here, we have identified a highly efficient small molecule, givinostat (Givi), a histone deacetylase inhibitor (HDACi) which is capable of transforming human iPSC into myogenic progenitor cells (MPC) that are highly proliferative and generate large numbers of extracellular vesicles (EV). Our “pharmacological reprogramming” approach using small molecules to generate MPC in a limited period of time and without use of viral vectors is a very significant step forward in cell-based therapy. We are proposing that iPSC pharmacologically reprogrammed into MPC with Givi will be optimally effective to regenerate sarcopenic muscle. In specific aim 1, the hypothesis that induced myogenic progenitor cells (iMPC) from iPSC with novel small molecules are effective and safe for regeneration of aged muscle will be tested; In specific Aim 2, the hypothesis that accelerated mobilization and engraftment of iMPC in an aged muscle microenvironment stimulate muscle regeneration will be tested; In specific Aim 3, the hypothesis that EV derived from Givi-induced MPC rejuvenate aged muscle and augment muscle regeneration will be tested. If many of the regenerative properties of iMPC can be credited to EV, there will be a paradigm shift in regenerative medicine to enable endogenous self-repair in sarcopenia by cell to cell transfer of proteins, mRNAs, and miRNAs (miRs) by EV. EV from engineered or modified stem cells are highly enriched with bioactive molecules including myogenic miRs responsible for activation of signaling pathways important in muscle regeneration. These studies will involve multidisciplinary approaches which will employ state of the art molecular biology, biochemical, histochemical, immunohistochemical techniques and integrative physiology involving well established experimental animal model and muscle function. This proposal is conceptually innovative because it addresses the structural and molecular characterization of iMPC and their EV and tests their role as key biological messengers of iMPC action in the treatment of sarcopenia.

Earlier awards

  • hiPS cells derived skeletal muscle progenitors and their extracellular vesicles for treatment of sarcopeniaFY 2024 · $308K
  • hiPS cells derived skeletal muscle progenitors and their extracellular vesicles for treatment of sarcopeniaFY 2024 · $307K
  • hiPS cells derived skeletal muscle progenitors and their extracellular vesicles for treatment of sarcopeniaFY 2023 · $307K