Acellular spinal cord scaffold seeded with mesenchymal stem cells promotes long-distance axon regeneration and functional recovery in spinal cord injured rats

Liu, Jia; Chen, Jian; Liu, Bin; Cs, Yang; Xie, Denghui; Zheng, Xiaochen; Xu, Song; Chen, Tianyu; Wang, Liang; Zhang, Zhongmin; Bai, Xia; Jin, Dadi

doi:10.1016/j.jns.2012.11.022

Cited by 76 publications

(53 citation statements)

References 45 publications

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“…10,11 In contrast to the extensive research on ECM scaffolds used for the reconstruction of various tissues, there are only a few studies addressing biological scaffolds for the repair of SCI based on an acellular muscle scaffold, 16 acellular sciatic nerve, 17 or acellular spinal cord scaffolds. 18 Nevertheless, the shape and conformation of such acellular scaffolds might be restrictive for bridging a chronic spinal cord lesion with an irregular cavity. Thus, in terms of suitability for clinical application, injectable in situ gelling hydrogels are more appropriate as these materials can easily conform to the lesion irregularity with minimal tissue damage during delivery.…”

mentioning

confidence: 99%

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair

Tukmachev

Forostyak

Kočí

et al. 2016

Tissue Engineering Part A

134

107

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Restoration of lost neuronal function after spinal cord injury (SCI) still remains a big challenge for current medicine. One important repair strategy is bridging the SCI lesion with a supportive and stimulatory milieu that would enable axonal rewiring. Injectable extracellular matrix (ECM)-derived hydrogels have been recently reported to have neurotrophic potential in vitro. In this study, we evaluated the presumed neuroregenerative properties of ECM hydrogels in vivo in the acute model of SCI. ECM hydrogels were prepared by decellularization of porcine spinal cord (SC) or porcine urinary bladder (UB), and injected into a spinal cord hemisection cavity. Histological analysis and real-time qPCR were performed at 2, 4, and 8 weeks postinjection. Both types of hydrogels integrated into the lesion and stimulated neovascularization and axonal ingrowth into the lesion. On the other hand, massive infiltration of macrophages into the lesion and rapid hydrogel degradation did not prevent cyst formation, which progressively developed over 8 weeks. No significant differences were found between SC-ECM and UB-ECM. Gene expression analysis revealed significant downregulation of genes related to immune response and inflammation in both hydrogel types at 2 weeks post SCI. A combination of human mesenchymal stem cells with SC-ECM did not further promote ingrowth of axons and blood vessels into the lesion, when compared with the SC-ECM hydrogel alone. In conclusion, both ECM hydrogels bridged the lesion cavity, modulated the innate immune response, and provided the benefit of a stimulatory substrate for in vivo neural tissue regeneration. However, fast hydrogel degradation might be a limiting factor for the use of native ECM hydrogels in the treatment of acute SCI.

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mentioning

confidence: 99%

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair

Tukmachev

Forostyak

Kočí

et al. 2016

Tissue Engineering Part A

134

107

View full text Add to dashboard Cite

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“…Many recent studies have used the acellular spinal cord (ASC) extracellular matrix as a cell carrier to investigate its therapeutic effect on neural recovery18. ASC scaffolds show good biocompatibility with the host tissue19.…”

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confidence: 99%

Thermo-sensitive hydrogels combined with decellularised matrix deliver bFGF for the functional recovery of rats after a spinal cord injury

Tian

et al. 2016

Sci Rep

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Because of the short half-life, either systemic or local administration of bFGF shows significant drawbacks to spinal injury. In this study, an acellular spinal cord scaffold (ASC) was encapsulated in a thermo-sensitive hydrogel to overcome these limitations. The ASC was firstly prepared from the spinal cord of healthy rats and characterized by scanning electronic microscopy and immunohistochemical staining. bFGF could specifically complex with the ASC scaffold via electrostatic or receptor-mediated interactions. The bFGF-ASC complex was further encapsulated into a heparin modified poloxamer (HP) solution to prepare atemperature-sensitive hydrogel (bFGF-ASC-HP). bFGF release from the ASC-HP hydrogel was more slower than that from the bFGF-ASC complex alone. An in vitro cell survival study showed that the bFGF-ASC-HP hydrogel could more effectively promote the proliferation of PC12 cells than a bFGF solution, with an approximate 50% increase in the cell survival rate within 24 h (P < 0.05). Compared with the bFGF solution, bFGF-ASC-HP hydrogel displayed enhanced inhibition of glial scars and obviously improved the functional recovery of the SCI model rat through regeneration of nerve axons and the differentiation of the neural stem cells. In summary, an ASC-HP hydrogel might be a promising carrier to deliver bFGF to an injured spinal cord.

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“…Several studies have demonstrated the ability of MSCs to preferentially migrate to sites of injury when infused in animal models (27–29). After receiving appropriate signals during tissue inflammation, MSCs could migrate to the lesions of the colon where they assisted in recovery, displaying high therapeutic potential with regards to tissue repair and/or the control of local inflammation (30).…”

Section: Discussionmentioning

confidence: 99%

Safety and therapeutic effect of mesenchymal stem cell infusion on moderate to severe ulcerative colitis

Hu¹,

Zhao²,

Zhang³

et al. 2016

Experimental and Therapeutic Medicine

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One of the primary targets of the clinical treatment of ulcerative colitis (UC) is to repair the damaged colonic mucosa. Mesenchymal stem cells (MSCs) have therapeutic potential in regenerative medicine due to their differentiation capacity and their secretion of numerous bioactive molecules. The present study describes a clinical trial (trial registration no. NCT01221428) investigating the safety and therapeutic effect of MSCs derived from human umbilical cord on moderate to severe UC. Thirty-four patients with UC were included in group I and treated with MSC infusion in addition to the base treatment, and thirty-six patients were in group II and treated with normal saline in addition to the base treatment. One month after therapy, 30/36 patients in group I showed good response, and diffuse and deep ulcer formation and severe inflammatory mucosa were improved markedly. During the follow up, the median Mayo score and histology score in group I were decreased while IBDQ scores were significantly improved compared with before treatment and group II (P<0.05). Compared with group II, there were no evident adverse reactions after MSC infusion in any of the patients in group I, and no chronic side effects or lingering effects appeared during the follow-up period. In conclusion, MSC infusion might be a useful and safe therapy for treating UC.

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Acellular spinal cord scaffold seeded with mesenchymal stem cells promotes long-distance axon regeneration and functional recovery in spinal cord injured rats

Cited by 76 publications

References 45 publications

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair

Thermo-sensitive hydrogels combined with decellularised matrix deliver bFGF for the functional recovery of rats after a spinal cord injury

Safety and therapeutic effect of mesenchymal stem cell infusion on moderate to severe ulcerative colitis

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