Increased proliferation of human synovial mesenchymal stem cells with autologous human serum: Comparisons with bone marrow mesenchymal stem cells and with fetal bovine serum

Abstract

Objective. Synovial mesenchymal stem cells (MSCs) are a promising cell source for cartilage regeneration due to their high chondrogenic potential. For clinical safety, autologous human serum should be used instead of fetal bovine serum (FBS). We undertook this study to compare the 2 types of serum for their enhancement of the proliferation and chondrogenic potentials of synovial MSCs and to investigate the mechanisms of the differences. Since effectiveness of the sera might depend on the origin of the MSCs, we also examined bone marrow MSCs.Methods. Synovium, bone marrow, and peripheral blood were obtained from 18 donors. Synovial and bone marrow MSCs were cultured with autologous human serum or FBS and analyzed. In addition, rabbit synovial MSCs cultured with autologous serum or FBS were transplanted into full-thickness cartilage defects of the knees of the same rabbits.Results. Human synovial MSCs expanded more in human serum than in FBS, and the opposite results were obtained with bone marrow MSCs. Hierarchical clustering analysis showed that the cell source, rather than the type of serum, affected the gene expression profile. Human serum contained high levels of plateletderived growth factor (PDGF), synovial MSCs expressed higher levels of PDGF receptor ␣ than did bone marrow MSCs, and neutralizing PDGF decreased the proliferation of synovial MSCs with autologous human serum. Although the in vitro chondrogenic potential of human synovial MSCs was affected by the serum source, the in vivo chondrogenic potential of rabbit synovial MSCs was similar in autologous serum and FBS groups.Conclusion. Autologous serum predominates in increasing the proliferation of synovial MSCs with chondrogenic potential through PDGF signaling.Mesenchymal stem cells (MSCs) have been fascinating for regenerative medicine because of their multidifferentiation potentials. MSCs from bone marrow, currently the most popular source, are usually expanded with fetal bovine serum (FBS) for research (1) and even for clinical use (2). However, supplementation with FBS carries several risks, such as disease transmission and immune reaction (3-6). Increasing the safety of medical treatments with MSCs requires the use of autologous human serum. Studies of bone marrow MSCs cultured with autologous human serum are still limited, and the usability of autologous human serum is

Cell-based Meniscal Tissue Engineering: A Case for Synoviocytes

“…These findings were further substantiated by Nimura et al who similarly determined that autologous serum enhances SMSC expansion but not in vivo chondrogenic transformation [63]. Interestingly, these researchers also found the mechanism by which the upregulated proliferation occurs is through platelet-derived growth factor (PDGF) for which the a-receptor expression in synovialderived MSC far surpasses bone marrow MSC [63]. PDGF is a known mitogenic and chemotactic stimulus and is present in high concentrations within fibrin clots, the most natural scaffold for wound healing, and thus is a powerful mediator for fibroblast recruitment and proliferation.…”

“…Tateishi and colleagues determined that culturing human SMSCs in human serum resulted in more rapid cellular proliferation but showed no difference in altering chondrogenic potential when compared with FBS [85]. These findings were further substantiated by Nimura et al who similarly determined that autologous serum enhances SMSC expansion but not in vivo chondrogenic transformation [63]. Interestingly, these researchers also found the mechanism by which the upregulated proliferation occurs is through platelet-derived growth factor (PDGF) for which the a-receptor expression in synovialderived MSC far surpasses bone marrow MSC [63].…”

“…Scaffolds may further be defined as ''smart scaffolds'' if they carry with them some type of signal that can direct appropriate tissue formation either from the implanted cell type or from the surrounding resident cellular population. With respect to the delivery of synoviocytes for cartilage (hyaline or fibrocartilage) engineering, a number of different systems have been investigated including hydrogels (alginate [53,66] collagen [51,63,94], and gellan [28]), pellet cultures [63,80], micromasses [3,66], small intestinal submucosa (SIS) [84], hyaluronan-based scaffolds (Hyaff-111; FAB, Abano Terme, Padova, Italy) [56], polyglycolic acid (PGA) [67,74], PGA/poly (L) lactic acid (PLLA) combinations [34], and scaffold-free cell infusions [44,60]. With relatively few studies directly comparing delivery methods, elucidating an optimal carrier or scaffold from the literature alone is difficult.…”

“…However, the surgical applicability of small spheroid pellets is somewhat limited for many large chondral applications. Hence, for articular cartilage, recent developments of a variety of hydrogel carriers that can suspend synoviocytes in three dimensions while filling discrete chondral defects have been investigated [28,51,53,63,66,94]. For meniscal applications, however, the need for tissue regeneration frequently resides in the avascular portion of the tissue, which may not exist as a singular defect with complete borders, thus posing a highly unstable and challenging environment for the surgical implantation of an engineered structure.…”

“…However, the initial cell growth media used by those investigators contained 10% FBS, the BMP-2 concentration used was lower, and the chondrogenic media they used contained dexamethasone [28]. Despite the controversy surrounding the concomitant use of the glucocorticoid dexamethasone and BMPs, numerous recent attempts to use SMSCs for articular cartilage engineering have used the combination of BMP-2, TGF-b3, and dexamethasone as a chondrogenic media in which to immerse three-dimensionally cultured synoviocytes, whether in pellets or collagen gels, all with promising results [50,63,80,94]. Because most of these strategies are geared toward the production of a hyalinelike articular cartilage, typical outcome measures include signaling or production of collagen Type II, aggrecan, and the activation of SOX-9.…”