Substance P improves MSC-mediated RPE regeneration by modulating PDGF-BB.

Area of Science:

• Regenerative Medicine
• Ophthalmology
• Stem Cell Biology

Background:

• Age-related macular degeneration (ARMD) and diabetic retinopathy impair retinal pigmented epithelium (RPE), necessitating RPE restoration for treatment.
• Mesenchymal stem cells (MSCs) show regenerative potential, but their efficacy can decline with prolonged ex vivo culture.
• Substance P (SP) is investigated for its role in enhancing MSC-mediated RPE regeneration.

Purpose of the Study:

• To investigate the effect of Substance P (SP) on bone marrow mesenchymal stem cell (MSC)-mediated retinal pigmented epithelium (RPE) regeneration in vitro.
• To evaluate how SP priming influences MSC conditioned medium (MSC-CM) effects on RPE viability, proliferation, and migration.
• To elucidate the underlying signaling pathways, specifically PDGF-BB secretion, involved in SP-mediated enhancement of MSC therapy.

Main Methods:

• Bone marrow mesenchymal stem cells (MSCs) were primed with Substance P (SP).
• Conditioned medium from SP-primed MSCs (MSC-SP-CM) was applied to RPE cells.
• RPE activity was assessed by measuring viability, proliferation, and migration.
• The role of PDGF-BB secretion and PDGF-PDGFR signaling was investigated.

Main Results:

• Ex vivo culture altered MSC characteristics, reducing viability and differentiation potential.
• Early passage MSC conditioned medium (E-MSC-CM) improved RPE viability and migration; late passage MSC conditioned medium (L-MSC-CM) had minimal effect.
• SP priming significantly enhanced the therapeutic effects of MSCs on RPE, especially in late passage cells.
• SP modulated PDGF-BB secretion in MSCs, suggesting a key mechanism for its restorative effects.

Conclusions:

• Substance P (SP) can restore the therapeutic efficacy of aged mesenchymal stem cells (MSCs) for treating retinal diseases.
• SP enhances MSCs' proliferative and paracrine activities, improving retinal pigmented epithelium (RPE) regeneration.
• The findings highlight the potential of SP as an adjunct therapy to improve stem cell treatments for ocular disorders via PDGF-PDGFR signaling.