Direct reprogramming of human bone marrow stromal cells into functional renal cells using cell-free extracts

Area of Science:

• Regenerative Medicine
• Cell Biology
• Nephrology

Background:

• Cell-based therapies are crucial for regenerative medicine.
• Bone marrow stromal cells (BMSCs) are a potential source for cell therapy.
• Developing functional kidney cells from stem cells is a significant challenge.

Purpose of the Study:

• To reprogram human bone marrow stromal cells (BMSCs) into renal proximal tubular-like epithelial cells.
• To assess the functional and structural characteristics of reprogrammed BMSCs.
• To evaluate the therapeutic potential of reprogrammed BMSCs in a preclinical model of acute kidney injury.

Main Methods:

• Human BMSCs were treated with cell-free extracts from HK2 cells.
• Morphological and functional assessments included dome formation, transepithelial resistance, albumin uptake, and marker expression (E-cadherin, aquaporin-1).
• Transmission electron microscopy and RNA sequencing were used for detailed structural and transcriptomic analysis. In vivo studies involved infusion into immunodeficient mice with cisplatin-induced acute kidney injury.

Main Results:

• Reprogrammed BMSCs exhibited morphological changes, including dome formation and tubule-like structures.
• Acquired epithelial functional properties and expressed specific renal markers (E-cadherin, aquaporin-1).
• In vivo studies showed engraftment, reduced renal injury, and improved kidney function in treated mice.

Conclusions:

• Human BMSCs can be effectively reprogrammed into functional renal proximal tubular-like epithelial cells using cell-free extracts.
• Reprogrammed BMSCs demonstrate potential for cell therapy in acute kidney injury.
• This study presents a promising cell resource for regenerative medicine applications in kidney disease.