Potential of secretome of fetal cartilage progenitor cells on regeneration of tissue; application to wound healing, hair growth and osteoarthritis

Author(s)
TRAN NGOC TRINH
Advisor
Byoung-Hyun Min
Department
일반대학원 분자과학기술학과
Publisher
The Graduate School, Ajou University
Publication Year
2023-08
Language
eng
Keyword
Anti-apoptosisAnti-inflammationFetal cartilage derived progenitor cellsHair lossOsteoarthritisSecretome
Alternative Abstract
Although tissue repair process is well known as characterization by four overlapping phases, including an early reaction to preserve homeostasis, an inflammatory reaction to protect against infection, a proliferative phase to rebuild the wound site, and a remodeling phase to restore tissue strength and function when tissue repair process is completed. In addition, all cells in each tissue of organs communicate with each other and are linked to the tissue repair process. Therefore, a drug that can act on all these tissues would be ideal. Theoretically, no single molecule can control inflammation and metabolism by acting on all cells in this manner. To date, many methods have been attempted to prevent the progression of damaged tissue, including pharmacological and nonpharmacological treatments, but none have been proven to be clinically effective yet. Therefore, biological therapies using cells and/or their secretome are expected to have considerable potential in this respect. <br>Recent studies have shown that the use of MSC secretome has been assessed to enhance the clinical applicability of this biological treatment as a true tissue repair agent/drug and to overcome the disadvantages of cell-based therapy while maintaining its advantages to their parent cells. Human fetal cartilage progenitor cells-secretome (ShFCPC) has shown potent anti-inflammatory and tissue-repair effects better than that of mesenchymal stem cells-secretome. However, its underlying mechanisms and effects on tissue repair process have rarely been systematically elucidated. Thus, the purpose of this study was to isolate and develop a ready-to-use product, novel non-immunogenic ShFCPC for clinical application, analyze molecular components within ShFCPC, and verify its tissue repair therapeutic efficacy. <br>In chapter I, we present a fabrication technology, including 3D pellet culture, filtration and lyophilization to produce a ready-to-use product, novel non-immunogenic ShFCPC containing superior quantity and quality of ECM molecules and bioactive molecules involving many cellular processes essential to homeostasis including the cell cycle, cell survival, inflammation, metabolism, and apoptosis. In addition, we first analyzed the secretome released by hFCPC, which was established by constructing, for the first time, an extensive map of the ShFCPC for supplying information on how they interact with biological pathways in tissue repair process. Thus, we suggest that ShFCPC could be a potential anti-inflammatory and anti-apoptotic agent for various stress microenvironment-related disorders. <br>In chapter II, we determined the potential utility of the identified proteins involved in inflammatory diseases such as osteoarthritis (OA) protection and validated their biological functions both in vitro and in vivo in an OA model are compared with those of human bone marrow-derived mesenchymal stem cells-secretome (ShBMSC) and hyaluronan (HA). Biological validation in vitro has shown that ShFCPC protects chondrocyte apoptosis by suppressing the expression of inflammatory mediators and matrix-degrading proteases and promotes the secretion of pro-chondrogenic cytokines in lipopolysaccharide-induced coculture of human chondrocytes and SW982 synovial cells compared with ShBMSC. Moreover, in a rat OA model, ShFCPC protects articular cartilage by reducing inflammatory cell infiltration and M1/M2 macrophage ratio in the synovium, by reducing inflammatory cell infiltration and M1/M2 macrophage ratio in the synovium, cartilage repair compared to ShBMSC and HA. Our findings support clinical translations of ShFCPC as a novel agent for modifying OA process. <br>In chapter III, as an extended clinical application of ShFCPC, we hypothesized that anti-apoptotic and tissue repair effects of ShFCPC could be suitable properties for hair loss treatment. Its useful properties are compared with those of minoxidil in terms of in vitro studies of dermal papilla (DP) cells behavior, hair follicle germ (HFG) formation, and ex vivo hair transplantation and in vivo hair loss model. hFCPC can alleviate hair loss by attenuating catabolism and apoptosis of DP cells. Furthermore, ShFCPC treatment is an effective therapeutic strategy to improve the hair repair process by cell-cell interactions between DP cells and epidermal cells creating a favorable environment for DP cells; this alters the local microenvironment and stimulates the activation of 𝛽-catenin signaling of DP cells repairing the damaged hair follies. These findings suggest that ShFCPC may be a novel regenerative agent suitable for hair repair and hair loss treatment.
URI
https://dspace.ajou.ac.kr/handle/2018.oak/24304
Fulltext

Appears in Collections:
Graduate School of Ajou University > Department of Molecular Science and Technology > 4. Theses(Ph.D)
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse