Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects: Does It Enhance Repair?
Abstract: The chondrogenic potential of culture-expanded bone-marrow-derived mesenchymal stem cells (BMDMSCs) is well described. Numerous studies have also shown enhanced repair when BMDMSCs, scaffolds, and growth factors are placed into chondral defects. Platelets provide a rich milieu of growth factors and, along with fibrin, are readily available for clinical use. The objective of this study was to determine if the addition of BMDMSCs to an autologous platelet-enriched fibrin (APEF) scaffold enhances chondral repair compared with APEF alone. Methods: A 15-mm-diameter full-thickness chondral defect was created on the lateral trochlear ridge of both stifle joints of twelve adult horses. In each animal, one defect was randomly assigned to receive APEF+BMDMSCs and the contralateral defect received APEF alone. Repair tissues were evaluated one year later with arthroscopy, histological examination, magnetic resonance imaging (MRI), micro-computed tomography (micro-CT), and biomechanical testing. Results: The arthroscopic findings, MRI T2 map, histological scores, structural stiffness, and material stiffness were similar (p > 0.05) between the APEF and APEF+BMDMSC-treated repairs at one year. Ectopic bone was observed within the repair tissue in four of twelve APEF+BMDMSC-treated defects. Defects repaired with APEF alone had less trabecular bone edema (as seen on MRI) compared with defects repaired with APEF+BMDMSCs. Micro-CT analysis showed thinner repair tissue in defects repaired with APEF+BMDMSCs than in those treated with APEF alone (p < 0.05). Conclusions: APEF alone resulted in thicker repair tissue than was seen with APEF+BMDMSCs. The addition of BMDMSCs to APEF did not enhance cartilage repair and stimulated bone formation in some cartilage defects. Conclusions: APEF supported repair of critical-size full-thickness chondral defects in horses, which was not improved by the addition of BMDMSCs. This work supports further investigation to determine whether APEF enhances cartilage repair in humans.
Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.
Publication Date: 2016-01-08 PubMed ID: 26738900PubMed Central: PMC4697360DOI: 10.2106/JBJS.O.00407Google Scholar: Lookup
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Summary
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The research article discusses a study that explored whether the addition of bone marrow-derived mesenchymal stem cells (BMDMSCs) to an autologous platelet-enriched fibrin (APEF) scaffold would enhance the repair of chondral defects (damage to cartilage) compared to using APEF alone. The study concluded that the addition of BMDMSCs did not markedly improve the results and, in some cases, even stimulated unwelcome bone formation in the cartilage defects.
Research Methodology
- The study involved creating full-thickness chondral defects of 15mm diameter on the stifle joints (equivalent to the human knee) of twelve adult horses. These defects were then treated with either APEF alone, or a combination of APEF and BMDMSCs.
- The treated areas were evaluated after a year using arthroscopy (examining joints using a type of endoscope), histological examination (looking at the microscopic structure of tissues), MRI scans, micro-computed tomography (a type of high-resolution 3D X-ray imaging), and biomechanical tests. Ectopic bone (bone growth in an abnormal location) was noted in four of the defects treated with the APEF + BMDMSCs combination.
Research Findings
- Comparison of the two treatment methods did not indicate any significant differences in arthroscopic findings, MRI T2 maps, histological scores, material stiffness, and structural stiffness after a one-year period.
- However, defects treated with the combined APEF and BMDMSCs treatment had thinner repair tissue and more trabecular bone edema (swelling caused by excess water) than those treated with APEF alone.
Conclusion
- The researchers found that the APEF scaffold was effective in the repair of critical-size full-thickness chondral defects in horses, but the addition of BMDMSCs did not enhance the cartilage repair.
- On the contrary, the addition of stem cells resulted in some unwanted bone formation and thinner repair tissue, recommending further investigation to determine whether APEF alone should be used to enhance cartilage repair in humans.
Cite This Article
APA
Goodrich LR, Chen AC, Werpy NM, Williams AA, Kisiday JD, Su AW, Cory E, Morley PS, McIlwraith CW, Sah RL, Chu CR.
(2016).
Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects: Does It Enhance Repair?
J Bone Joint Surg Am, 98(1), 23-34.
https://doi.org/10.2106/JBJS.O.00407 Publication
Researcher Affiliations
- Gail Holmes Equine Orthopedic Research Center, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523.
- Department of Bioengineering, Mail Code 0412, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412.
- Large Animal Clinical Sciences, 2015 S.W. 16th Avenue, Gainesville, FL 32608.
- Department of Orthopedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063.
- Gail Holmes Equine Orthopedic Research Center, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523.
- Department of Bioengineering, Mail Code 0412, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412.
- Department of Bioengineering, Mail Code 0412, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412.
- Gail Holmes Equine Orthopedic Research Center, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523.
- Gail Holmes Equine Orthopedic Research Center, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523.
- Department of Bioengineering, Mail Code 0412, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412.
- Department of Orthopedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063. chucr@stanford.edu.
MeSH Terms
- Animals
- Arthroscopy / methods
- Biopsy, Needle
- Blood Platelets
- Cartilage Diseases / pathology
- Cartilage Diseases / surgery
- Cartilage, Articular / pathology
- Cartilage, Articular / surgery
- Disease Models, Animal
- Fibrin / administration & dosage
- Fibrin / pharmacology
- Follow-Up Studies
- Horses
- Humans
- Immunohistochemistry
- Magnetic Resonance Imaging / methods
- Mesenchymal Stem Cell Transplantation / methods
- Random Allocation
- Tissue Engineering / methods
- Tissue Scaffolds
- Transplantation, Autologous
- Treatment Outcome
Grant Funding
- R01 AR052784 / NIAMS NIH HHS
- R01 AR051963 / NIAMS NIH HHS
- R01 AR044058 / NIAMS NIH HHS
- RC2 AR058929 / NIAMS NIH HHS
- 1K08AR054903-01A2 / NIAMS NIH HHS
- P01 AG007996 / NIA NIH HHS
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