Lentiviral Gene Therapy for Bone Repair Using Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells

Overview

Journal Hum Gene Ther

Specialties Genetics
Pharmacology

Date 2019 Feb 19

PMID 30773946

Citations 9

Authors

Sofia Bougioukli

Biagio Saitta

Osamu Sugiyama

Amy H Tang

Joseph Elphingstone

Denis Evseenko

Jay R Lieberman

Affiliations

Soon will be listed here.

Abstract

Umbilical cord blood (UCB) has been increasingly explored as an alternative source of stem cells for use in regenerative medicine due to several advantages over other stem-cell sources, including the need for less stringent human leukocyte antigen matching. Combined with an osteoinductive signal, UCB-derived mesenchymal stem cells (MSCs) could revolutionize the treatment of challenging bone defects. This study aimed to develop an regional gene-therapy strategy using -transduced allogeneic UCB-MSCs to promote bone repair. To this end, human UCB-MSCs were transduced with a lentiviral vector carrying the cDNA for (LV-BMP-2). assays to determine the UCB-MSC osteogenic potential and BMP-2 production were followed by implantation of LV-BMP-2-transduced UCB-MSCs in a mouse hind-limb muscle pouch. Non-transduced and LV-GFP-transduced UCB-MSCs were used as controls. Transduction with LV-BMP-2 was associated with abundant BMP-2 production and induction of osteogenic differentiation . Implantation of -transduced UCB-MSCs led to robust heterotopic bone formation 4 weeks postoperatively, as seen on radiographs and histology. These results, along with the fact that UCB-MSCs can be easily collected with no donor-site morbidity and low immunogenicity, suggest that UCB might be a preferable allogeneic source of MSCs to develop an gene-therapy approach to treat difficult bone-repair scenarios.

Citing Articles

Regional Gene Therapy for Bone Tissue Engineering: A Current Concepts Review.

Gallo M, Elias A, Reynolds J, Ball J, Lieberman J Bioengineering (Basel). 2025; 12(2).

PMID: 40001640 PMC: 11852166. DOI: 10.3390/bioengineering12020120.

Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating Neuroinflammation.

Gao Q, Gao Z, Su M, Huang Y, Zhang C, Li C Stem Cells Int. 2023; 2023:8887091.

PMID: 38020203 PMC: 10663085. DOI: 10.1155/2023/8887091.

Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment.

Cabrera-Perez R, Rafols-Mitjans A, Roig-Molina A, Beltramone S, Vives J, Batlle-Morera L J Transl Med. 2023; 21(1):802.

PMID: 37950242 PMC: 10638709. DOI: 10.1186/s12967-023-04672-9.

The Combination of Platelet Rich Plasma Gel, Human Umbilical Mesenchymal Stem Cells and Nanohydroxyapatite/polyamide 66 Promotes Angiogenesis and Bone Regeneration in Large Bone Defect.

Liu W, Huang Y, Liu D, Zeng T, Wang J, Li A Tissue Eng Regen Med. 2022; 19(6):1321-1336.

PMID: 36074328 PMC: 9679130. DOI: 10.1007/s13770-022-00471-3.

LINC02381, a sponge of miR-21, weakens osteogenic differentiation of hUC-MSCs through KLF12-mediated Wnt4 transcriptional repression.

Zhao G, Luo W, Yuan Y, Lin F, Guo L, Ma J J Bone Miner Metab. 2021; 40(1):66-80.

PMID: 34778905 DOI: 10.1007/s00774-021-01277-4.

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