Autologous hematopoietic stem cell transplantation modifies specific aspects of systemic sclerosis-related microvasculopathy.

Autor:	Santana-Gonçalves M; Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Zanin-Silva D; Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Henrique-Neto Á; Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Moraes DA; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Kawashima-Vasconcelos MY; Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Lima-Júnior JR; Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Dias JBE; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Bragagnollo V; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., de Azevedo JTC; Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Covas DT; Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Malmegrim KCR; Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Ramalho L; Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Brazil., Oliveira MC; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Avenida dos Bandeirantes, 3900, 14048-900 Ribeirão Preto, Brazil.
Jazyk:	angličtina
Zdroj:	Therapeutic advances in musculoskeletal disease [Ther Adv Musculoskelet Dis] 2022 Mar 28; Vol. 14, pp. 1759720X221084845. Date of Electronic Publication: 2022 Mar 28 (Print Publication: 2022).
DOI:	10.1177/1759720X221084845
Abstrakt:	Objective: Autologous hematopoietic stem cell transplantation (AHSCT) is a therapeutic option for patients with severe and progressive systemic sclerosis (SSc). Here, we aimed to investigate how AHSCT affects the vasculopathy of SSc patients. Methods: Twenty-seven SSc patients were retrospectively assessed, before and after AHSCT, for vessel morphology (nailfold capillaroscopy), skin expression of endothelial markers and serum levels of markers of inflammation, angiogenesis and endothelial activation. Skin biopsies were analyzed by immunohistochemistry (IHC) for expression of CD31, VE-cadherin, E-selectin, angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), Tie-2, vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), and endothelin-1 before and 12 months post-AHSCT. Serum samples from SSc patients were assessed before and up to 36 months after AHSCT for IL-6, von Willebrand factor (vWF), CXC Motif Chemokine Ligand 8 (CXCL8), Endothelin-1, epidermal growth factor (EGF), VEGFA, Pentraxin-3, Intercellular Adhesion Molecule 1 (ICAM-1), E-selectin, P-selectin, Thrombomodulin and IL-18 levels, and compared to healthy control samples. Results: On nailfold capillaroscopy, the number of capillaries increased at 1 year, while giant capillaries decreased at 6 months and 1 year after AHSCT. In the skin biopsies, expression of E-selectin notably decreased and Ang1 increased after AHSCT. At baseline, all vascular markers evaluated in the serum were significantly higher in SSc patients when compared to healthy controls, except for ICAM-1. When compared at different time points after AHSCT, Thrombomodulin, Pentraxin-3, vWF, and IL-18 levels remained generally stable at high levels until 36 months after AHSCT. Conclusion: Our results suggest that AHSCT contributes to improvements of the vessel morphology and dermal microvasculopathy, but does not normalize elevated levels of serum vascular markers in SSc patients. Additional vascular therapeutic approaches might contribute to more effectively treat the endothelial injury. Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. (© The Author(s), 2022.)
Databáze:	MEDLINE
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