Biofabrication of an in-vitro bone model for Gaucher disease.

Autor:	Banerjee D; Engineering Science and Mechanics Department, Penn State University, University Park, PA, United States of America.; Department of Medicine, Division of Cardiology, University of California, San Diego, La Jolla, CA, United States of America., Ivanova MM; Lysosomal & Rare Disorders Research & Treatment Center-LDRTC, Fairfax, VA, United States of America., Celik N; Engineering Science and Mechanics Department, Penn State University, University Park, PA, United States of America., Kim MH; Department of Biomedical Engineering, Pennsylvania State University, University Park, PA, United States of America., Derman ID; Engineering Science and Mechanics Department, Penn State University, University Park, PA, United States of America., Limgala RP; Lysosomal & Rare Disorders Research & Treatment Center-LDRTC, Fairfax, VA, United States of America., Ozbolat IT; Engineering Science and Mechanics Department, Penn State University, University Park, PA, United States of America.; Department of Biomedical Engineering, Pennsylvania State University, University Park, PA, United States of America.; The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, United States of America.; Materials Research Institute, Pennsylvania State University, University Park, PA, United States of America.; Department of Neurosurgery, Pennsylvania State College of Medicine, Hershey, PA, United States of America.; Medical Oncology, Cukurova University, Adana, Turkey.; Biotechnology Research and Application Center, Cukurova University, Adana, Turkey., Goker-Alpan O; Lysosomal & Rare Disorders Research & Treatment Center-LDRTC, Fairfax, VA, United States of America.
Jazyk:	angličtina
Zdroj:	Biofabrication [Biofabrication] 2023 Sep 22; Vol. 15 (4). Date of Electronic Publication: 2023 Sep 22.
DOI:	10.1088/1758-5090/acf95a
Abstrakt:	Gaucher disease (GD), the most prevalent lysosomal disorder, is caused by GBA1 gene mutations, leading to deficiency of glucocerebrosidase, and accumulation of glycosphingolipids in cells of the mononuclear phagocyte system. While skeletal diseases are the leading cause of morbidity and reduced quality of life in GD, the pathophysiology of bone involvement is not yet fully understood, partly due to lack of relevant human model systems. In this work, we present the first 3D human model of GD using aspiration-assisted freeform bioprinting, which enables a platform tool with a potential for decoding the cellular basis of the developmental bone abnormalities in GD. In this regard, human bone marrow-derived mesenchymal stem cells (obtained commercially) and peripheral blood mononuclear cells derived from a cohort of GD patients, at different severities, were co-cultured to form spheroids and differentiated into osteoblast and osteoclast lineages, respectively. Co-differentiated spheroids were then 3D bioprinted into rectangular tissue patches as a bone tissue model for GD. The results revealed positive alkaline phosphatase (ALP) and tartrate-resistant ALP activities, with multi-nucleated cells demonstrating the efficacy of the model, corroborating with gene expression studies. There were no significant changes in differentiation to osteogenic cells but pronounced morphological deformities in spheroid formation, more evident in the 'severe' cohort, were observed. Overall, the presented GD model has the potential to be adapted to personalized medicine not only for understanding the GD pathophysiology but also for personalized drug screening and development. (Creative Commons Attribution license.)
Databáze:	MEDLINE
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