About This Project

Bone loss in HIV, COVID-19, rheumatoid arthritis, and osteoporosis is linked to damaged mitochondria in bone cells. Current therapies target the matrix but not the dysfunctional cells that perpetuate the damage. Our project uses mesenchymal stem cells to deliver healthy mitochondria, restoring energy production and cellular function — a regenerative strategy to reverse bone degeneration at its root.

Ask the Scientists

What is the context of this research?

This project integrates infectious diseases, bioenergetics, and regenerative medicine. HIV, COVID-19, rheumatoid arthritis, and osteoporosis damage bone by impairing mitochondrial function in bone cells, disrupting formation–resorption balance and increasing fracture risk. Current therapies target bone matrix but cannot repair damaged cells. We propose to use human umbilical cord–derived MSCs (UC-MSCs) to transfer healthy mitochondria into bone cells, restoring energy and function. UC-MSCs are non-invasively obtained, widely available, expand robustly in vitro, and provide high-quality neonatal mitochondria. Their immunomodulatory and low-immunogenic profile supports safe allogeneic use, reduces inflammation, and promotes mitochondrial transfer. By targeting the root cause, this therapy could reverse bone degeneration across diseases, improving outcomes and quality of life.

What is the significance of this project?

The significance of this project lies in its potential to transform how bone diseases linked to infections and chronic conditions are treated. Unlike current therapies that only address the bone matrix and fail to repair the underlying cellular damage, this project targets the fundamental cause—mitochondrial dysfunction in bone cells. By restoring healthy mitochondria through stem cell–mediated transfer, the approach can reactivate bone regeneration, halt disease progression, and reduce long-term complications like fractures. This novel strategy could benefit millions affected by HIV, COVID-19, rheumatoid arthritis, osteoporosis, and other bone disorders, offering a durable, regenerative therapy that improves bone health and patient quality of life.

What are the goals of the project?

Isolate and expand human umbilical cord–derived MSCs (UC-MSCs) from postnatal cords, as was previously performed in our laboratory.

Precondition UC-MSCs withresveratrol (10 μM, 48 h) to enhance PGC-1α–mediated mitochondrial biogenesis and quality.

Co-culture treated UC-MSCs with HIV-damaged primary osteoblasts derived from MSCs (as was described in our laboratory) to promote mitochondrial transfer via direct contact and tunneling nanotubes.

Verify transfer using MitoTracker labeling, confocal microscopy, and flow cytometry. Positive control: healthy MSCs; negative: MSCs pre-treated with mitochondrial inhibitors (e.g., rotenone) or fixed MSCs.

Assess recovery by ATP production (luminescence), ROS quantification, and bone markers (ALP for osteoblasts), comparing results to uninfected healthy cells (baseline) and untreated HIV-damaged cells (negative control).