Fetal Cartilage Progenitor Cells in the Repair of Osteochondral Defects

Background:. Therapies for cartilage restoration are of great interest, but current options provide limited results. In salamanders, interzone (IZN) tissue can regenerate large joint lesions. The mammalian homolog to this tissue exists during fetal development and exhibits remarkable chondrogenesis...

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Main Authors: Bruno C. Menarim, DVM, PhD, Chan Hee Mok, PhD, Kirsten E. Scoggin, PhD, Alexis Gornik, DVM, Emma N. Adam, DVM, PhD, Shavahn C. Loux, PhD, James N. MacLeod, VMD, PhD
Format: Article
Language:English
Published: Wolters Kluwer 2025-03-01
Series:JBJS Open Access
Online Access:http://journals.lww.com/jbjsoa/fulltext/10.2106/JBJS.OA.24.00043
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author Bruno C. Menarim, DVM, PhD
Chan Hee Mok, PhD
Kirsten E. Scoggin, PhD
Alexis Gornik, DVM
Emma N. Adam, DVM, PhD
Shavahn C. Loux, PhD
James N. MacLeod, VMD, PhD
author_facet Bruno C. Menarim, DVM, PhD
Chan Hee Mok, PhD
Kirsten E. Scoggin, PhD
Alexis Gornik, DVM
Emma N. Adam, DVM, PhD
Shavahn C. Loux, PhD
James N. MacLeod, VMD, PhD
author_sort Bruno C. Menarim, DVM, PhD
collection DOAJ
description Background:. Therapies for cartilage restoration are of great interest, but current options provide limited results. In salamanders, interzone (IZN) tissue can regenerate large joint lesions. The mammalian homolog to this tissue exists during fetal development and exhibits remarkable chondrogenesis in vitro. This study analyzed the potential of equine IZN and adjacent anlagen (ANL) cells to regenerate osteochondral defects. Methods:. Osteochondral defects were created in the knee of immunosuppressed rats and were grafted with cell pellets from either equine fetal IZN, equine fetal ANL, adult fibroblasts, or adult chondrocytes, or they were left untreated. Osteochondral repair was assessed after 2, 6, and 16 weeks. Results:. Untreated lesions unexpectedly failed to represent critical-sized defects and at 2 weeks exhibited new subchondral bone covered by a fibrocartilage layer that thinned over time. Fibroblast-treated defects filled with soft fibrous tissue. Chondrocyte-treated repair tissue exhibited strong proteoglycan and COL2 staining but poor integration to the adjacent bone. Defects treated with IZN, ANL, or chondrocyte pellets developed hyaline cartilage with increasing safranin-O and collagen II staining over time. IZN and ANL repair tissues exhibited some evidence of zonal architecture such as native cartilage and the best bone integration; nonetheless, they developed exuberant growth, often causing patellar instability and osteoarthritis. Conclusions:. IZN or ANL cells exhibited some potential to recapitulate developmental features during cartilage repair. However, identifying regulatory determinants of IZN and ANL-derived overgrowths is necessary. Clinical Relevance:. Studies grafting IZN or ANL tissues in larger animal models with regular immune functions may provide additional insights into improving osteochondral regeneration.
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spelling doaj-art-c4292ab5fd9843a1bb122b841ce916ed2025-01-24T09:20:07ZengWolters KluwerJBJS Open Access2472-72452025-03-0110110.2106/JBJS.OA.24.00043JBJSOA2400043Fetal Cartilage Progenitor Cells in the Repair of Osteochondral DefectsBruno C. Menarim, DVM, PhD0Chan Hee Mok, PhD1Kirsten E. Scoggin, PhD2Alexis Gornik, DVM3Emma N. Adam, DVM, PhD4Shavahn C. Loux, PhD5James N. MacLeod, VMD, PhD61 Gluck Equine Research Center, Department of Veterinary Science, Martin-Gatton College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky2 Department of Orthopedic Surgery, School of Medicine, University of California San Francisco, San Francisco, California1 Gluck Equine Research Center, Department of Veterinary Science, Martin-Gatton College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky3 College of Veterinary Medicine, Lincoln Memorial University, Harrogate, Tennessee1 Gluck Equine Research Center, Department of Veterinary Science, Martin-Gatton College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky1 Gluck Equine Research Center, Department of Veterinary Science, Martin-Gatton College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky1 Gluck Equine Research Center, Department of Veterinary Science, Martin-Gatton College of Agriculture, Food and Environment, University of Kentucky, Lexington, KentuckyBackground:. Therapies for cartilage restoration are of great interest, but current options provide limited results. In salamanders, interzone (IZN) tissue can regenerate large joint lesions. The mammalian homolog to this tissue exists during fetal development and exhibits remarkable chondrogenesis in vitro. This study analyzed the potential of equine IZN and adjacent anlagen (ANL) cells to regenerate osteochondral defects. Methods:. Osteochondral defects were created in the knee of immunosuppressed rats and were grafted with cell pellets from either equine fetal IZN, equine fetal ANL, adult fibroblasts, or adult chondrocytes, or they were left untreated. Osteochondral repair was assessed after 2, 6, and 16 weeks. Results:. Untreated lesions unexpectedly failed to represent critical-sized defects and at 2 weeks exhibited new subchondral bone covered by a fibrocartilage layer that thinned over time. Fibroblast-treated defects filled with soft fibrous tissue. Chondrocyte-treated repair tissue exhibited strong proteoglycan and COL2 staining but poor integration to the adjacent bone. Defects treated with IZN, ANL, or chondrocyte pellets developed hyaline cartilage with increasing safranin-O and collagen II staining over time. IZN and ANL repair tissues exhibited some evidence of zonal architecture such as native cartilage and the best bone integration; nonetheless, they developed exuberant growth, often causing patellar instability and osteoarthritis. Conclusions:. IZN or ANL cells exhibited some potential to recapitulate developmental features during cartilage repair. However, identifying regulatory determinants of IZN and ANL-derived overgrowths is necessary. Clinical Relevance:. Studies grafting IZN or ANL tissues in larger animal models with regular immune functions may provide additional insights into improving osteochondral regeneration.http://journals.lww.com/jbjsoa/fulltext/10.2106/JBJS.OA.24.00043
spellingShingle Bruno C. Menarim, DVM, PhD
Chan Hee Mok, PhD
Kirsten E. Scoggin, PhD
Alexis Gornik, DVM
Emma N. Adam, DVM, PhD
Shavahn C. Loux, PhD
James N. MacLeod, VMD, PhD
Fetal Cartilage Progenitor Cells in the Repair of Osteochondral Defects
JBJS Open Access
title Fetal Cartilage Progenitor Cells in the Repair of Osteochondral Defects
title_full Fetal Cartilage Progenitor Cells in the Repair of Osteochondral Defects
title_fullStr Fetal Cartilage Progenitor Cells in the Repair of Osteochondral Defects
title_full_unstemmed Fetal Cartilage Progenitor Cells in the Repair of Osteochondral Defects
title_short Fetal Cartilage Progenitor Cells in the Repair of Osteochondral Defects
title_sort fetal cartilage progenitor cells in the repair of osteochondral defects
url http://journals.lww.com/jbjsoa/fulltext/10.2106/JBJS.OA.24.00043
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