Restoration of cellular function of mesenchymal stem cells from a hypophosphatasia patient

Gene Therapy
Y KatsubeH Ohgushi

Abstract

Mesenchymal stem cells (MSCs) can differentiate into multiple cell lineages and are used for regenerative treatments for a variety of diseases. However, the patient's cells cannot be used to treat genetic diseases. Allogeneic cells can serve as an alternative but long-term survival is uncertain. Our experience of allo-transplantation to a patient with hypophosphatasia, which is caused by mutations of the tissue non-specific alkaline phosphatase (TNSALP) gene resulting in low serum alkaline phosphatase (ALP) activity and skeletal deformity, did not improve these clinical characteristics. Therefore, we sought to use autologous MSCs for the treatment of hypophosphatasia. MSCs derived from the patient's bone marrow had a similar profile when compared with well-reported MSCs. However, the MSCs had extremely low ALP activity and could not produce a mineralized bone matrix even under the osteogenic culture conditions. We therefore transduced a retroviral vector with TNSALP promoter-driven TNSALP gene in the MSCs. In the culture condition, the MSCs had about 7-fold higher ALP activity than did mock-transduced MSCs, and showed mineralization as well as bone-specific markers. Furthermore, the MSCs, but not mock-transduced MSCs, newly for...Continue Reading

References

Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·M J WeissH Harris
Jun 1, 1996·The Journal of Clinical Endocrinology and Metabolism·M P WhyteC S Hill
Apr 2, 1999·Science·M F PittengerD R Marshak
May 20, 1999·Human Molecular Genetics·L ZurutuzaE Mornet
Nov 11, 1999·Journal of Biomedical Materials Research·H Ohgushi, A I Caplan
Oct 12, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·C WennbergJ L Millán
May 30, 2001·Trends in Molecular Medicine·A I Caplan, S P Bruder
Aug 18, 2001·Arthritis and Rheumatism·C De BariF P Luyten
Jun 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·Edwin M HorwitzTed Hofmann
Apr 4, 2003·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Michael P WhytePaul L Martin
Feb 21, 2004·Science·Joel R ChamberlainDavid W Russell
Mar 7, 2006·Biochemical and Biophysical Research Communications·Etsuko IkedaHajime Ohgushi
May 24, 2007·The Journal of Clinical Endocrinology and Metabolism·Richard A CahillMichael P Whyte

❮ Previous
Next ❯

Citations

Dec 7, 2013·Expert Opinion on Biological Therapy·Hajime Ohgushi
Mar 15, 2014·The International Journal of Artificial Organs·Genti ShytiPaolo Giannoni
Jul 10, 2019·Science Advances·Tomoaki IwayamaShinya Murakami
Sep 25, 2017·Metabolism: Clinical and Experimental·Etienne Mornet

❮ Previous
Next ❯

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Related Papers

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
J L MillánMichael P Whyte
The Journal of Clinical Endocrinology and Metabolism
Richard A CahillMichael P Whyte
The Journal of Clinical Endocrinology and Metabolism
Michael P WhyteChad Deal
Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Michael P WhytePaul L Martin
© 2022 Meta ULC. All rights reserved