Human Synovial Mesenchymal Stem Cells Good Manufacturing Practices for Articular Cartilage Regeneration

Author(s)

Fernandes, Tiago Lazzaretti ^{[1, 2]} ; Kimura, Heitor Akio ^[1] ; Gomes Pinheiro, Carla Cristina ^[1] ; Shimomura, Kazunori ^[3] ; Nakamura, Norimasa ^[4] ; Ferreira, Jose Ricardo ^[5] ; Gomoll, Andreas H. ^[6] ; Hernandez, Arnaldo Jose ^{[1, 2]} ; Bueno, Daniela Franco ^[1]

Affiliation

^[1] Hosp Sirio Libanes, Inst Ensino & Pesquisa, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sports Med Grp, Inst Orthoped & Traumatol, Hosp Clin HCFMUSP, Fac Med, 333 Dr Ovidio Pires de Campos, BR-05403010 Sao Paulo - Brazil

^[3] Osaka Univ, Dept Orthopaed Surg, Grad Sch Med, Osaka - Japan

^[4] Osaka Univ, Ctr Adv Med Engn & Informat, Osaka - Japan

^[5] Mil Inst Engn IME, Dept Mat Sci, Post Grad Programme Mat Sci, Rio De Janeiro - Brazil

^[6] Hosp Special Surg, Orthoped Surg & Sports Med, 535 E 70th St, New York, NY 10021 - USA

• Document type: Journal article
• Source: TISSUE ENGINEERING PART C-METHODS; v. 24, n. 12, p. 709-716, DEC 1 2018.
• Web of Science Citations: 4

Abstract

Background: Cartilage restoration is a desperately needed bridge for patients with symptomatic cartilage lesions. Chondral lesion is a pathology with high prevalence, reaching as much as 63% of general population and 36% among athletes. Despite autologous chondrocyte implantation versatility, it still fails to fully reproduce hyaline articular cartilage characteristics. Mesenchymal stem cells (MSCs) may be isolated from various known tissues, including discarded fragments at arthroscopy such as synovial membrane. Choice of harvesting site is motivated by MSCs' abilities to modulate immunologic and inflammatory response through paracrine communication. Synovial MSCs have a greater proliferation and strong chondrogenic potential than bone and adipose MSCs and a less hypertrophic differentiation than bone MSCs. Good manufacturing practice (GMP) laboratory techniques for human clinical trials are still novel. To our knowledge, there are only two clinical trials in humans published since today. Purpose: Therefore, this work aimed to isolate and characterize synovial MSCs and evaluated their differentiation properties according to GMP standards. Materials and Methods: One-gram tissue sample from three patients of synovia was harvested at the beginning of arthroscopy surgery. MSCs were isolated, expanded, and characterized by flow cytometry. Results: It was possible to isolate and expand MSCs cultures from synovia, characterize MSCs by flow cytometry using proper monoclonal antibodies, and differentiate MSCs by coloring technique after chondrogenic, adipogenic, and osteogenic differentiations. Cartilage treatment may benefit from these tissue engineering protocols since arthroscopic procedures are routinely performed for different purposes in a previous stage and a favorable chondronegic differentiation cell lineage may be collected and stored in a less invasive way. Conclusion: Laboratory protocols established according to presented GMP were able to isolate and characterize MSCs obtained from synovia. (AU)

• FAPESP's process: 17/05774-5 - Comparison of tissue engineered construct (TEC) derived of human stem cells from dental pulp and synovia on articular cartilage regeneration: a translational study
• Grantee: Tiago Lazzaretti Fernandes
• Support Opportunities: Regular Research Grants