Decellularized Disc Hydrogels for hBMSCs tissue-specific differentiation and tissue regeneration.

Area of Science:

• Biomaterials Science
• Stem Cell Biology
• Tissue Engineering

Background:

• Tissue specificity of decellularized tissue matrices (DTMs) influences cell fate, particularly mesenchymal stem cell differentiation.
• Cell fate is governed by the microenvironment, including material composition and spatial features.

Purpose of the Study:

• To investigate the tissue-specific effects of decellularized nucleus pulposus (DNP-G) and annulus fibrosus (DAF-G) hydrogels on human bone marrow mesenchymal stem cell (hBMSC) fate and in vivo regeneration.
• To elucidate the role of the integrin-mediated RhoA/LATS/YAP1 signaling pathway in DTM-induced stem cell differentiation.

Main Methods:

• Proteomic analysis to identify distinct protein compositions of DNP-G and DAF-G.
• In vitro culturing of hBMSCs with DNP-G (3D) and DAF-G (2D) to assess cell differentiation.
• In vivo studies using rat models of nucleus pulposus degeneration and annulus fibrosus defects.

Main Results:

• DNP-G promoted NP-like differentiation, while DAF-G induced AF-like differentiation in hBMSCs, correlating with native tissue microenvironments.
• Integrin-mediated RhoA/LATS/YAP1 signaling was activated in DAF-G (2D)-induced AF differentiation, with YAP1 activation playing a key role.
• DNP-G and DAF-G demonstrated specific efficacy in promoting tissue regeneration in respective intervertebral disc degeneration models.

Conclusions:

• Tissue-specific DTMs (DNP-G and DAF-G) can precisely control stem cell fate through compositional and spatial cues.
• The integrin-mediated RhoA/LATS/YAP1 pathway is crucial for DTM-driven stem cell differentiation and tissue regeneration.
• Tissue-specific DTMs offer a promising strategy for advanced treatments of intervertebral disc degeneration.