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Regenerative Therapy by Suprachoroidal Cell Autograft in Dry Age-related Macular Degeneration: Preliminary In Vivo Report

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Capillary regeneration in scleroderma: stem cell therapy reverses phenotype?

Jo N Fleming¹, Richard A Nash, D O McLeod

¹Department of Pathology, University of Washington, Seattle, Washington, United States of America. flemij@u.washington.edu

|January 17, 2008

Summary

Scleroderma causes capillary loss and altered vessel markers. Treatment reversed these vascular changes, suggesting a reversible mechanism for the disease's vascular component.

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Published on: January 20, 2014

Area of Science:

Vascular Biology
Autoimmune Diseases
Dermatology

Background:

Scleroderma is an autoimmune disease characterized by significant vascular pathology.
This vasculopathy is a primary driver of scleroderma's clinical symptoms.

Purpose of the Study:

To investigate the capillary rarefaction in scleroderma.
To identify molecular changes in endothelial cells within scleroderma skin.
To assess the reversibility of scleroderma vasculopathy after treatment.

Main Methods:

Immunohistochemistry and mRNA in situ hybridization on skin biopsies from scleroderma patients and controls.
Morphometric analysis to quantify capillary density.
Comparison of molecular markers before and after high-dose immunosuppressive therapy and autologous hematopoietic cell transplant.

Main Results:

Scleroderma exhibits true capillary rarefaction (loss of capillaries).
Residual vessels show altered endothelial cell phenotype, with loss of vascular endothelial cadherin and overexpression of interferon alpha and RGS5.
Treatment led to clinical improvement, increased capillary counts, and normalization of vascular endothelial cadherin, interferon alpha, and RGS5 expression.

Conclusions:

This study provides objective evidence of reversible capillary loss in scleroderma.
Changes in vascular endothelial cadherin, interferon alpha, and RGS5 are implicated in the vascular component of scleroderma.
Findings may inform treatments for other capillary-loss conditions like hypertension and heart failure.