Evaluation of alginate hydrogel encapsulated mesenchymal stem cell migration in horses.
Abstract: Osteoarthritis is an incapacitating disease characterized by pain and a progressive decrease in joint mobility. The implantation of mesenchymal stem cells (MSCs) has shown promising results for its treatment. The challenge remains to keep the cells longer at the site of action, increasing their therapeutic potential. The aim of this study was to evaluate the effectiveness of the Qtracker® 655 nanocrystal marking on allogeneic synovial membrane (SM) MSCs, encapsulated in alginate hydrogel, evaluating the migration of these cells. The 10 radiocarpal joints were submitted to arthroscopic surgery (D0), divided into two groups. The chondral defect was treated according to the group: GA free-labelled MSC and GB labelled MSC microcapsules. Seven days after lesion induction and implantation of labelled cells, biopsies of the lesion site were performed in two animals, and fragments of SM and joint capsule also collected, which were frozen and later processed for fluorescence microscopy. The synovial fluid of the three animals was analyzed by flow cytometry three times - 3, 7 and 21 days after application. The cellular marking with the nanocrystals allowed the visualization of the cells in cartilage, synovial membrane, synovial fluid and articular capsule, but with a predilection for the synovial membrane and the lesion site was scarce. The labelled MSC in microcapsules were scarce in the synovial fluid and could be related to the small quantity of MSCs leaving the pores of the microcapsules, also favorable results, as the cells release paracrine effects acting for a long period until the cellular differentiation.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Publication Date: 2019-02-25 PubMed ID: 30826587DOI: 10.1016/j.rvsc.2019.02.005Google Scholar: Lookup
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Summary
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The research study aimed to evaluate the effectiveness of using a specific type of marking on mesenchymal stem cells (MSCs) for osteoarthritis treatment in horses. The stem cells, encapsulated in a material called an alginate hydrogel, were implanted into horses to observe cell migration patterns and their retention at the site of the injury.
Overview of the Study
- The study was motivated by the need to improve osteoarthritis treatment approaches. Osteoarthritis is a debilitating disease defined by pain and decreased joint mobility. Treating this disease with implantations of MSCs has demonstrated promising outcomes, but maintaining the cells at the action site to increase their therapeutic potential has been challenging.
- Mesenchymal stem cells are multi-potent cells that can differentiate into a variety of cell types. These cells were marked with Qtracker® 655 nanocrystals and encapsulated in an alginate hydrogel – a water-based, biocompatible material often used in drug delivery and tissue engineering.
- After the treatment, ten radiocarpal joints underwent arthroscopic surgery to allow for the evaluation of MSC migration. The joints were segregated into two groups based on their treatment: one receiving free-labelled MSCs (GA) and the other receiving labelled MSCs in microcapsules (GB).
Methodology and Results
- Seven days post-lesion induction and cell implantation, tissue samples from two animals were collected, including from the lesion site and parts of the joint. These samples were processed for fluorescence microscopy.
- In addition, the synovial fluid of three animals was analyzed to study the distribution of the labelled MSCs in the joint fluid over time, at 3, 7, and 21 days after the cell application.
- The marking method facilitated the visualization of cells in several locations (cartilage, synovial membrane, joint fluid, and articular capsule); however, the cells were mostly found in the synovial membrane with a sparse presence at the lesion site.
- Scarcely, the labelled MSCs in microcapsules were observed in the synovial fluid, which could be related to the lower number of MSCs escaping from the microcapsule pores. This result was seen as positive, given that encapsulated stem cells can release healing factors over an extended period until the cells differentiate.
Implications of the Study
- The use of an alginate hydrogel for encapsulating MSCs, as shown in this study, might be an efficient strategy to increase the dwell time and therapeutic potential of the stem cells at the lesion site.
- The findings could be leveraged to refine stem cell therapies used in treating osteoarthritis in horses, potentially improving cell survival, proliferation, and migration.
- More broadly, the results could also inform the design of stem cell-based treatments for other diseases and species, optimizing cell delivery and harnessing the therapeutic potential stem cells offer.
Cite This Article
APA
Santos VHD, Pfeifer JPH, Souza JB, Stievani FC, Hussni CA, Golim MA, Deffune E, Alves ALG.
(2019).
Evaluation of alginate hydrogel encapsulated mesenchymal stem cell migration in horses.
Res Vet Sci, 124, 38-45.
https://doi.org/10.1016/j.rvsc.2019.02.005 Publication
Researcher Affiliations
- Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
- Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
- Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
- Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
- Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
- School of Medicine, Blood Centre Division, São Paulo State University (UNESP), Botucatu, SP, Brazil.
- School of Medicine, Blood Centre Division, São Paulo State University (UNESP), Botucatu, SP, Brazil.
- Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil. Electronic address: ana.liz@unesp.br.
MeSH Terms
- Alginates / administration & dosage
- Animals
- Arthroscopy / veterinary
- Cell Movement
- Female
- Horse Diseases / therapy
- Horses
- Hydrogels / administration & dosage
- Male
- Mesenchymal Stem Cells / physiology
- Osteoarthritis / therapy
- Osteoarthritis / veterinary
- Synovial Membrane / cytology
Citations
This article has been cited 5 times.- Duan WL, Zhang LN, Bohara R, Martin-Saldaña S, Yang F, Zhao YY, Xie Y, Bu YZ, Pandit A. Adhesive hydrogels in osteoarthritis: from design to application. Mil Med Res 2023 Jan 30;10(1):4.
- de Souza JB, Rosa GDS, Rossi MC, Stievani FC, Pfeifer JPH, Krieck AMT, Bovolato ALC, Fonseca-Alves CE, Borrás VA, Alves ALG. In Vitro Biological Performance of Alginate Hydrogel Capsules for Stem Cell Delivery. Front Bioeng Biotechnol 2021;9:674581.
- Fülber J, Agreste FR, Seidel SRT, Sotelo EDP, Barbosa ÂP, Michelacci YM, Baccarin RYA. Chondrogenic potential of mesenchymal stem cells from horses using a magnetic 3D cell culture system. World J Stem Cells 2021 Jun 26;13(6):645-658.
- Hiruthyaswamy SP, Bose A, Upadhyay A, Raha T, Bhattacharjee S, Singha I, Ray S, Nicky Macarius NM, Viswanathan P, Deepankumar K. Molecular signaling pathways in osteoarthritis and biomaterials for cartilage regeneration: a review. Bioengineered 2025 Dec;16(1):2501880.
- Pfeifer JPH, Stievani FC, Fernandes CJDC, Rosa GDS, Apolonio EVP, Rossi MC, Zambuzzi WF, Alves ALG. Influence of inflammation on the expression of microRNA-140 in extracellular vesicles from 2D and 3D culture models of synovial-membrane-derived stem cells. Front Bioeng Biotechnol 2024;12:1416694.
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