Next Generation Mesenchymal Stem Cell (MSC)–Based Cartilage Repair Using Scaffold-Free Tissue Engineered Constructs Generated with Synovial Mesenchymal Stem Cells

Shimomura, Kazunori; Ando, Wataru; Moriguchi, Yu; Sugita, Norihiko; Yasui, Yukihiko; Koizumi, Keiichi; Fujie, Hiromichi; Hart, David A.; Yoshikawa, Hideki; Nakamura, Norimasa

doi:10.1177/1947603515571002

Cited by 47 publications

(41 citation statements)

References 89 publications

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“…ACI is a two-step procedure that consists of healthy cartilage harvesting through arthroscopy followed by the expanded cell culture and, in a second step, cartilage defect filling (13)(14)(15). In spite of second and third ACI generations' versatility, those techniques use healthy cartilage tissue, "in vitro" related chondrocytes dedifferentiation and still fails to fully reproduce the hyaline characteristics of the original articular cartilage (6,13,(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

“…More recently, mesenchymal stem cell-based therapy has received considerable attention, because of the feasibility of handling the tissue harvest and ex vivo cell expansion and differentiation (12,13). Moreover, these cells present minor immunological rejection due to the low surface expression of major histocompatibility complex (MHC) antigens, efficient engraftment and long-term coexistence in the host, which turns them an attractive therapeutic option (18,19).…”

Section: Introductionmentioning

confidence: 99%

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Macrophage: A Potential Target on Cartilage Regeneration

et al. 2020

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Cartilage lesions and osteoarthritis (OA) presents an ever-increasing clinical and socioeconomic burden. Synovial inflammation and articular inflammatory environment are the key factor for chondrocytes apoptosis and hypertrophy, ectopic bone formation and OA progression. To effectively treat OA, it is critical to develop a drug that skews inflammation toward a pro-chondrogenic microenvironment. In this narrative and critical review, we aim to see the potential use of immune cells modulation or cell therapy as therapeutic alternatives to OA patients. Macrophages are immune cells that are present in synovial lining, with different roles depending on their subtypes. These cells can polarize to pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, being the latter associated with wound-healing by the production of ARG-1 and pro-chondrogenic cytokines, such as IL-10, IL-1RA, and TGF-b. Emerging evidence reveals that macrophage shift can be determined by several stimuli, apart from the conventional in vitro IL-4, IL-13, and IL-10. Evidences show the potential of physical exercise to induce type 2 response, favoring M2 polarization. Moreover, macrophages in contact with oxLDL have effect on the production of anabolic mediators as TGF-b. In the same direction, type II collagen, that plays a critical role in development and maturation process of chondrocytes, can also induce M2 macrophages, increasing TGF-b. The mTOR pathway activation in macrophages was shown to be able to polarize macrophages in vitro, though further studies are required. The possibility to use mesenchymal stem cells (MSCs) in cartilage restoration have a more concrete literature, besides, MSCs also have the capability to induce M2 macrophages. In the other direction, M1 polarized macrophages inhibit the proliferation and viability of MSCs and impair their ability to immunosuppress the environment, preventing cartilage repair. Therefore, even though MSCs therapeutic researches advances, other sources of M2 polarization are attractive issues, and further studies will contribute to the possibility to manipulate this polarization and to use it as a therapeutic approach in OA patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Macrophage: A Potential Target on Cartilage Regeneration

et al. 2020

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“…SMSCs are an emerging cell source for regenerative medicine applications, including for bone 29,30 and cartilage [24][25][26][27] applications. The long-term goal of this work was to identify scaffold-based biochemical cues capable of guiding zonallytailored SMSC differentiation for OCD repair.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22][23] In addition, although bone marrow MSC responses to a range of scaffold-based biochemical stimuli have been systematically examined, SMSC responses to 3D scaffold formulations are just beginning to be understood and characterized. For example, a majority of the work with SMSCs has focused on chondrogenic applications with scaffold-free approaches 24,25 or using a variety of different scaffolds, including collagen 26 and gelatin-dextran. 27 However, studies which allow comparison of SMSC differentiation in response to defined scaffold-based biochemical signals are limited, 28 as are reports of scaffold-based SMSC osteogenic differentiation.…”

Section: Introductionmentioning

confidence: 99%

Toward zonally tailored scaffolds for osteochondral differentiation of synovial mesenchymal stem cells

et al. 2018

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Synovium-derived mesenchymal stem cells (SMSCs) are an emerging cell source for regenerative medicine applications, including osteochondral defect (OCD) repair. However, in contrast to bone marrow MSCs, scaffold compositions which promote SMSC chondrogenesis/osteogenesis are still being identified. In the present manuscript, we examine poly(ethylene) glycol (PEG)-based scaffolds containing zonally-specific biochemical cues to guide SMSC osteochondral differentiation. Specifically, SMSCs were encapsulated in PEG-based scaffolds incorporating glycosaminoglycans (hyaluronan or chondroitin-6-sulfate [CSC]), low-dose of chondrogenic and osteogenic growth factors (TGFβ1 and BMP2, respectively), or osteoinductive poly(dimethylsiloxane) (PDMS). Initial studies suggested that PEG-CSC-TGFβ1 scaffolds promoted enhanced SMSC chondrogenic differentiation, as assessed by significant increases in Sox9 and aggrecan. Conversely, PEG-PDMS-BMP2 scaffolds stimulated increased levels of osteoblastic markers with significant mineral deposition. A “Transition” zone formulation was then developed containing a graded mixture of the chondrogenic and osteogenic signals present in the PEG-CSC-TGFβ1 and PEG-PDMS-BMP2 constructs. SMSCs within the “Transition” formulation displayed a phenotypic profile similar to hypertrophic chondrocytes, with the highest expression of collagen X, intermediate levels of osteopontin, and mineralization levels equivalent to “bone” formulations. Overall, these results suggest that a graded transition from PEG-CSC-TGFβ1 to PEG-PDMS-BMP2 scaffolds elicits a gradual SMSC phenotypic shift from chondrocyte to hypertrophic chondrocyte to osteoblast-like. As such, further development of these scaffold formulations for use in SMSC-based OCD repair is warranted.

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“…Such autologous synovial MSCs were applied to cartilage injury 29. Currently, only one clinical study repairing chondral defect using scaffold-free three-dimensional tissue engineered construct, derived from human synovial MSCs, was completed in March 2015; but, the outcomes of the study were not reported 30,31. This may be considered to be evident that these naturally occurring MSCs may play an important role in meniscal healing and regeneration.…”

Section: Introductionmentioning

confidence: 99%

Potential use of mesenchymal stem cells in human meniscal repair: current insights

Pak

Lee²,

Park³

et al. 2017

OAJSM

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The menisci of the human knee play an important role in maintaining normal functions to provide stability and nutrition to the articular cartilage, and to absorb shock. Once injured, these important structures have very limited natural healing potential. Unfortunately, the traditional arthroscopic meniscectomy performed on these damaged menisci may predispose the joint toward early development of osteoarthritis. Although a very limited number of studies are available, mesenchymal stem cells (MSCs) have been investigated as an alternative therapeutic modality to repair human knee meniscal tears. This review summarizes the results of published applications of MSCs in human patients, which showed that the patients who received MSCs (autologous adipose tissue-derived stem cells or culture-expanded bone marrow-derived stem cells) presented symptomatic improvements, along with magnetic resonance imaging evidences of the meniscal repair.

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Next Generation Mesenchymal Stem Cell (MSC)–Based Cartilage Repair Using Scaffold-Free Tissue Engineered Constructs Generated with Synovial Mesenchymal Stem Cells

Cited by 47 publications

References 89 publications

Macrophage: A Potential Target on Cartilage Regeneration

Macrophage: A Potential Target on Cartilage Regeneration

Toward zonally tailored scaffolds for osteochondral differentiation of synovial mesenchymal stem cells

Potential use of mesenchymal stem cells in human meniscal repair: current insights

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