Genipin cross-linked type II collagen/chondroitin sulfate composite hydrogel-like cell delivery system induces differentiation of adipose-derived stem cells and regenerates degenerated nucleus pulposus

Zhou, Xiaopeng; Wang, Jingkai; Fang, Weijing; Tao, Yiqing; Zhao, Tengfei; Xia, Kaishun; Liang, Chengzhen; Hua, Jianming; Li, Fangcai

doi:10.1016/j.actbio.2018.03.019

Cited by 98 publications

(68 citation statements)

References 70 publications

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“…83 Biomaterials as delivery vehicles, and in particular hydrogels, have been utilized to overcome retention issues and provide additional support for cell survival and phenotype retention. [84][85][86][87][88][89] Injectable biomaterial systems utilizing alginates, collagens, hyaluronic acid, fibrin and a variety of other substances have all shown promise for improving cell delivery for disc repair [90][91][92] ; however, for clinical translation, the biomaterial itself will require regulatory approval.…”

Section: Effective Cell Delivery and Retentionmentioning

confidence: 99%

Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section

et al. 2018

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Intervertebral disc degeneration is strongly associated with chronic low back pain, a leading cause of disability worldwide. Current back pain treatment approaches (both surgical and conservative) are limited to addressing symptoms, not necessarily the root cause. Not surprisingly therefore, long‐term efficacy of most approaches is poor. Cell‐based disc regeneration strategies have shown promise in preclinical studies, and represent a relatively low‐risk, low‐cost, and durable therapeutic approach suitable for a potentially large patient population, thus making them attractive from both clinical and commercial standpoints. Despite such promise, no such therapies have been broadly adopted clinically. In this perspective we highlight primary obstacles and provide recommendations to help accelerate successful clinical translation of cell‐based disc regeneration therapies. The key areas addressed include: (a) Optimizing cell sources and delivery techniques; (b) Minimizing potential risks to patients; (c) Selecting physiologically and clinically relevant efficacy metrics; (d) Maximizing commercial potential; and (e) Recognizing the importance of multidisciplinary collaborations and engaging with clinicians from inception through to clinical trials.

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Section: Effective Cell Delivery and Retentionmentioning

confidence: 99%

Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section

et al. 2018

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“…The integral MFAT is superior to separated cells and fat because the ECM and fat in MFAT have the ability to fill space, and the cells in MFAT decrease inflammation and improve the matrix synthesis function of native NPCs. Our previous study demonstrated that simple space-filling material is not able to regenerate the degenerated NP and that simple cells do not survive well in the microenvironment of degenerative NP 13 . Therefore, we think the regenerative effects in the degenerated NP depend on the integral MFAT.…”

Section: Discussionmentioning

confidence: 98%

Micro Fragmented Adipose Tissue Promotes the Matrix Synthesis Function of Nucleus Pulposus Cells and Regenerates Degenerated Intervertebral Disc in a Pig Model

et al. 2020

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Intervertebral disc (IVD) degeneration and consequent lower back pain is a common disease. Micro fragmented adipose tissue (MFAT) is promising for a wide range of applications in regenerative medicine. In this study, MFAT was isolated by a nonenzymatic method and co-cultured with nucleus pulposus cells (NPCs) using an indirect co-culture system in vitro. A pig disc degeneration model was used to investigate the regenerative effect of MFAT on degenerated IVDs in vivo. The mRNA expression of Sox9, Acan, and Col2 in NPCs was significantly increased, while no significant increase was observed in the mRNA expression of proinflammatory cytokine genes after the NPCs were co-cultured with MFAT. Nucleus pulposus (NP)-specific markers were increased in MFAT cells after co-culture with NPCs. After injection of MFAT, the disc height, water content, extracellular matrix, and structure of the degenerated NP were significantly improved. MFAT promoted the matrix synthesis function of NPCs, and NPCs stimulated the NP-like differentiation of MFAT cells. In addition, MFAT also partly regenerated degenerated IVDs in the pig model.

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“…However, their biocompatibility and potential cytotoxicity limit their applications. On the other hand, natural materials, including collagen (Zhou et al, 2018c), fibrin (Long et al, 2018), HA (Kazezian et al, 2017), and chitosan (Doench et al, 2019), provide cells with adhesive surfaces and have low cytotoxicity, thus possessing good cellular compatibility. Therefore, the combination of these two types of materials is a potential approach to fabricate bioscaffolds with reliable mechanical properties and biological compatibility (Frith et al, 2013).…”

Section: Biosynthetic Materialsmentioning

confidence: 99%

“…Collagen type II alone has been shown to induce ADSC differentiation into NP-like cells (Zhou et al, 2018b), which was related to FoxA2 overexpression (Zhou et al, 2018a). Moreover, Collagen type II combined with other natural components and crosslinkers, such as chondroitin sulfate (Zhou et al, 2018c), hyaluronan (Calderon et al, 2010), genipin (Zhou et al, 2018b), N,N-(3-dimethylaminopropyl)-N -ethylcarbodiimide and N-hydroxysuccinimide (EDAC/NHS) , to modify its porosity and other micromechanical properties has also been shown to exert an improved effect on stem cell proliferation and directional differentiation.…”

Section: Biochemical Componentsmentioning

confidence: 99%

Biomaterials-Induced Stem Cells Specific Differentiation Into Intervertebral Disc Lineage Cells

Peng

Huang

Liu

et al. 2020

Front. Bioeng. Biotechnol.

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Stem cell therapy, which promotes stem cells differentiation toward specialized cell types, increases the resident population and production of extracellular matrix, and can be used to achieve intervertebral disc (IVD) repair, has drawn great attention for the development of IVD-regenerating materials. Many materials that have been reported in IVD repair have the ability to promote stem cells differentiation. However, due to the limitations of mechanical properties, immunogenicity and uncontrollable deviations in the induction of stem cells differentiation, there are few materials that can currently be translated into clinical applications. In addition to the favorable mechanical properties and biocompatibility of IVD materials, maintaining stem cells activity in the local niche and increasing the ability of stem cells to differentiate into nucleus pulposus (NP) and annulus fibrosus (AF) cells are the basis for promoting the application of IVDregenerating materials in clinical practice. The purpose of this review is to summarize IVD-regenerating materials that focus on stem cells strategies, analyze the properties of these materials that affect the differentiation of stem cells into IVD-like cells, and then present the limitations of currently used disc materials in the field of stem cell therapy and future research perspectives.

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Genipin cross-linked type II collagen/chondroitin sulfate composite hydrogel-like cell delivery system induces differentiation of adipose-derived stem cells and regenerates degenerated nucleus pulposus

Cited by 98 publications

References 70 publications

Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section

Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section

Micro Fragmented Adipose Tissue Promotes the Matrix Synthesis Function of Nucleus Pulposus Cells and Regenerates Degenerated Intervertebral Disc in a Pig Model

Biomaterials-Induced Stem Cells Specific Differentiation Into Intervertebral Disc Lineage Cells

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