Designer Self-Assembling Peptide Nanofiber Scaffolds Containing Link Protein N-Terminal Peptide Induce Chondrogenesis of Rabbit Bone Marrow Stem Cells

Wang, Baichuan; Sun, Caixia; Shao, Zengwu; Yang, Shuai; Che, Biao; Wu, Qiang; Liu, Jianxiang

doi:10.1155/2014/421954

Cited by 23 publications

(22 citation statements)

References 34 publications

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“…Therefore, constructing a tissue engineering matrix material with a suitable structure and biological activity, and providing an appropriate stromal environment for IVD stem/progenitor cells are two important methods of effective treatments for IVD degeneration 96e100 . Polypeptide self-assembled nanofiber gels are one of the latest materials in tissue engineering 42,99,101 . They have been used for three-dimensional culture of cells, repair of defective tissue, and drug/cytokine release.…”

Section: Constructing a Tissue Engineering Matrix Materials With A Suimentioning

confidence: 99%

Mechanisms of endogenous repair failure during intervertebral disc degeneration

Ma¹,

Chen²,

et al. 2019

Osteoarthritis and Cartilage

104

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Intervertebral disc (IVD) degeneration is frequently associated with Low back pain (LBP), which can severely reduce the quality of human life and cause enormous economic loss. However, there is a lack of long-lasting and effective therapies for IVD degeneration at present. Recently, stem cell based tissue engineering techniques have provided novel and promising treatment for the repair of degenerative IVDs. Numerous studies showed that stem/progenitor cells exist naturally in IVDs and could migrate from their niche to the IVD to maintain the quantity of nucleus pulposus (NP) cells. Unfortunately, these endogenous repair processes cannot prevent IVD degeneration as effectively as expected. Therefore, theoretical basis for regeneration of the NP in situ can be obtained from studying the mechanisms of endogenous repair failure during IVD degeneration. Although there have been few researches to study the mechanism of cell death and migration of stem/progenitor cells in IVD so far, studies demonstrated that the major inducing factors (compression and hypoxia) of IVD degeneration could decrease the number of NP cells by regulating apoptosis, autophagy, and necroptosis, and the particular chemokines and their receptors played a vital role in the migration of mesenchymal stem cells (MSCs). These studies provide a clue for revealing the mechanisms of endogenous repair failure during IVD degeneration. This article reviewed the current research situation and progress of the mechanisms through which IVD stem/progenitor cells failed to repair IVD tissues during IVD degeneration. Such studies provide an innovative research direction for endogenous repair and a new potential treatment strategy for IVD degeneration.

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Section: Constructing a Tissue Engineering Matrix Materials With A Suimentioning

confidence: 99%

Mechanisms of endogenous repair failure during intervertebral disc degeneration

Ma¹,

Chen²,

et al. 2019

Osteoarthritis and Cartilage

104

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show abstract

“…We and others have previously demonstrated that Link N can act as an anabolic agent in the disc enhancing proteoglycan synthesis and depleting proteinase expression. [34][35][36][37][38]44,45,48,[52][53][54][55][56][57][58][59][60] We have shown that Link N can maintain its anabolic effects in an inflammatory milieu when human IVD cells were exposed to IL-1. 36 Using a rabbit model of IVD degeneration, we have generated data indicative of the role of Link N and Short Link N, a recently discovered fragment of the Link N peptide, in disc repair.…”

Section: Discussionmentioning

confidence: 99%

“…In Table 1, we show that Link N is an ideal IVD target profile based on the present study and other published work. [35][36][37]45,[52][53][54][55][56][57][58][59][60] In Table 2, a summary of the clinical and market opportunities for Link N is presented.…”

Section: Discussionmentioning

confidence: 99%

Link N as a therapeutic agent for discogenic pain

et al. 2018

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Neurotrophins (NTs) are the major contributors of sensory axonal sprouting, neural survival, regulation of nociceptive sensory neurons, inflammatory hyperalgesia, and neuropathic pain. Intervertebral disc (IVD) cells constitutively express NTs. Their expression is upregulated by proinflammatory cytokines present in the IVD during degeneration, which can promote peripheral nerve ingrowth and hyperinnervation, leading to discogenic pain. Currently, there are no targeted therapies that decrease hyperinnervation in degenerative disc disease. Link N is a naturally occurring peptide with a high regenerative potential in the IVD. Therefore, the suitability of Link N as a therapeutic peptide for suppressing NTs, which are known modulators and mediators of pain, was investigated. The aim of the present study is to determine the effect of Link N on NTs expression, nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF), and their cognate receptors TrkA and TrkB as they are directly correlated with symptomatic back pain. Furthermore, the neurotransmitter (substance P) was also evaluated in human annulus fibrosus (AF) cells stimulated with cytokines. Human AF cells isolated from normal IVDs were stimulated with interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α) in the presence or absence of Link N. NGF release in the media was evaluated by Western blotting. Total RNA was isolated and gene expression was measured using real‐time PCR. Gene expression of NGF, BDNF, TrkA, and TrkB significantly decreased in human disc cells stimulated with either IL‐1β or TNF‐α supplemented with Link N when compared to the cells stimulated only with IL‐1β or TNF‐α. NGF protein expression was also suppressed in AF cells coincubated with Link N and IL‐1β when compared to the cells stimulated only with IL‐1β. Link N can suppress the stimulation of NGF, BDNF, and their receptors TrkA and TrkB in AF cells in an inflammatory milieu. Thus, coupled with previous observations, this suggests that administration of Link N has the potential to not only repair the discs in early stages of the disease but also suppress pain.

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“…[22][23][24][25] They are capable of self-replication and differentiation into osteocytes in appropriate culture conditions and can contribute to the regeneration of mesenchymal tissues such as bone. [3,26] BM-MSCs can be rapidly expanded ex vivo without loss of their multi-lineage differentiation potential. [13] They are readily available and amenable to genetic manipulation.…”

Section: Discussionmentioning

confidence: 99%

Tissue engineering using mesenchymal stem cells with periosteal wrap for bone defect repair in rabbits

Thua¹,

Pham²,

Lê³

et al. 2015

Plast Aesthet Res

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Aim: Mesenchymal stem cells (MSCs) are an excellent potential source of cells for bone tissue engineering due to their excellent renewal ability and osteogenic differentiation capabilities. This study was designed to evaluate the bone formation properties of a demineralized cancellous bone scaffold seeded with MSCs, with or without periosteum, in a critical size bone defect model in rabbits. Methods: Rabbit culture-expanded bone marrow (BM)-MSCs were seeded onto a human demineralized cancellous bone (HDCB) scaffold. Bone defects measuring 15 mm in length were created in each radius. A total of 56 bone defects in 28 rabbits were randomly assigned to one of the 4 groups for scaffold implantation: Group 1: HDCB graft only; Group 2: periosteum-wrapped HDCB graft; Group 3: HDCB graft seeded with BM-MSCs and Group 4: periosteum-wrapped HDCB graft seeded with BM-MSCs. All rabbits were sacrificed 12 weeks after surgery for gross observation, radiological assessment, histological analyses and biomechanical measurements. Results: New bone (NB) formation and bone healing were successfully achieved, both radiologically and histologically, on demineralized cancellous bone graft seeded with BM-MSCs. Results were improved when BM-MSCs were associated with periosteum. Conclusion: This study demonstrates that repair of bone defects in a rabbit model can be achieved through bone grafting using BM-MSCs, implanted on a demineralized cancellous bone scaffold. The formation of NB was optimized when combined with the preservation of periosteum at the site of injury.

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Designer Self-Assembling Peptide Nanofiber Scaffolds Containing Link Protein N-Terminal Peptide Induce Chondrogenesis of Rabbit Bone Marrow Stem Cells

Cited by 23 publications

References 34 publications

Mechanisms of endogenous repair failure during intervertebral disc degeneration

Mechanisms of endogenous repair failure during intervertebral disc degeneration

Link N as a therapeutic agent for discogenic pain

Tissue engineering using mesenchymal stem cells with periosteal wrap for bone defect repair in rabbits

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