EFFECT OF INTRAARTICULAR INJECTION OF MICROCAPSULES WITH MESENCHYMAL STEM CELLS ON THE TREATMENT OF OSTEOARTHRITIS

• Grant number: 17/14460-4
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2017
• End date: October 31, 2019
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
• Principal Investigator: Ana Liz Garcia Alves
• Grantee: Ana Liz Garcia Alves
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Mesenchymal stem cells (MSC) have been used in the treatment of osteoarthritis (OA), with satisfactory outcomes. However, a major problem that must be overcome before it can be effectively implemented into the clinical setting is a suitable delivery system that can retain an optimal quantity of the cells at the articular joint for a maximal clinical benefits system that will give a mechanical as well as an immune protection for the foreign cells, while at the same time enhancing the yields of differentiated cells, maintaining cell microenvironments and sustaining the differentiated cell functions. MSC encapsulation has been proven a promising approach for therapeutic agents delivery. However, in intra-articular applications there is a dispersion of the cells and their viability reduction, as well as a clear understanding about the migration capacity of CTMMS to the injured sites. Therefore, the aim of this study will be to investigate the action of CTMMS protected in microcapsules in vitro and in vivo, searching for the best approach for OA treatment. The behavior of CTMMS labeled with Qtracker 655 nanocrystals after intra-articular application in experimentally induced chondral defects in horses will also be studied. Fifteen animals will undergo arthroscopic surgery (D0), where a chondral lesion will be induced in the medial trochlea of the talus of the pelvic member. These joints will be divided into three groups: GA, GB and GC, where GA will receive free labeled CTMMS, GB microcapsules with labeled CTMMS and GC will not receive treatment. Previous tests will be carried out on the feasibility and characterization of CTMMS. After lesion induction and implantation of labeled cells, biopsies of the lesion site, the synovial membrane and the joint capsule will be performed at two moments (D7 and D14), followed by histological processing for fluorescence microscopy analysis. The synovial fluid of the animals also will be analyzed by physical, chemical, cytological and flow cytometry tests at three moments, 3, 7 and 14 days after application. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ROSA, GUSTAVO DOS SANTOS; TERAMOTO KRIECK, ANDRE MASSAHIRO; PADULA, ENRICO TOPAN; STIEVANI, FERNANDA DE CASTRO; ROSSI, MARIANA CORREA; HUBBE PFEIFER, JOAO PEDRO; BASSO, ROBERTA MARTINS; MARQUES BRAZ, ALINE MARCIA; GOLIM, MARJORIE DE ASSIS; GARCIA ALVES, ANA LIZ. Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration. FRONTIERS IN IMMUNOLOGY, v. 13, p. 12-pg., 2022-04-27. (17/14460-4, 17/12815-0)

DE SOUZA, JAQUELINE BRANDAO; ROSA, GUSTAVO DOS SANTOS; ROSSI, MARIANA CORREA; STIEVANI, FERNANDA DE CASTRO; PFEIFER, JOAO PEDRO HUBBE; TERAMOTO KRIECK, ANDRE MASSAHIRO; DE CARVALHO BOVOLATO, ANA LIVIA; FONSECA-ALVES, CARLOS EDUARDO; AMIGO BORRAS, VICENTE; GARCIA ALVES, ANA LIZ. In Vitro Biological Performance of Alginate Hydrogel Capsules for Stem Cell Delivery. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, v. 9, AUG 27 2021. (17/01369-9, 17/12815-0, 17/14460-4)

ROSA, GUSTAVO; KRIECK, ANDRE MASSAHIRO TERAMOTO; PADULA, ENRICO; PFEIFER, JOAO PEDRO HUBBE; SOUZA, JAQUELINE BRANDAO DE; ROSSI, MARIANA; STIEVANI, FERNANDA; DEFFUNE, ELENICE; TAKAHIRA, REGINA; ALVES, ANA LIZ GARCIA. Allogeneic synovial membrane-derived mesenchymal stem cells do not significantly affect initial inflammatory parameters in a LPS-induced acute synovitis model. Research in Veterinary Science, v. 132, p. 485-491, OCT 2020. (17/14460-4)

DIAS, CAROLINA DA SILVA; ROSSI, MARIANA CORREA; APOLONIO, EMANUEL V. P.; ROSA, GUSTAVO DOS SANTOS; HUBBE PFEIFER, JOAO PEDRO; HUSSNI, CARLOS ALBERTO; WATANABE, MARCOS JUN; ALVES, ANA LIZ GARCIA. Low Mg content on Ti-Nb-Sn alloy when in contact with eBMMSCs promotes improvement of its biological functions. JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, v. 32, n. 12, DEC 2021. (19/09752-1, 17/14460-4, 17/13876-2)