Tissue engineered regeneration of completely transected spinal cord using human mesenchymal stem cells

Kang, Kkot Nim; Kim, Da Yeon; Yoon, So Mi; Lee, Ju Young; Lee, Bit Na; Kwon, Jin Seon; Seo, Hyo Won; Lee, Il Woo; Shin, Ha Cheol; Kim, Young Man; Kim, Hyun Soo; Kim, Jae Ho; Min, Byoung Hyun; Lee, Hai Bang; Kim, Moon Suk

doi:10.1016/j.biomaterials.2012.03.043

Cited by 56 publications

(31 citation statements)

References 45 publications

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“…8 Therefore, as an alternative to nerve autografts, artificial peripheral nerve guidance conduits (NGCs) have been made to mimic nerve autografts. [9][10][11][12][13][14] Many kinds of artificial peripheral NGCs have been developed by using different biomaterials. [9][10][11][12][13][14][15][16][17][18] With the development of various biomaterials and fabrication techniques during the previous decades, NGCs have been greatly improved to satisfy the requirement of easy fabrication, reproducibility or availability for mass production, suturability, sterilizability, along with proper mechanical properties to resist collapsing when applied to in vivo implantation and regeneration.…”

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confidence: 99%

“…[9][10][11][12][13][14] Many kinds of artificial peripheral NGCs have been developed by using different biomaterials. [9][10][11][12][13][14][15][16][17][18] With the development of various biomaterials and fabrication techniques during the previous decades, NGCs have been greatly improved to satisfy the requirement of easy fabrication, reproducibility or availability for mass production, suturability, sterilizability, along with proper mechanical properties to resist collapsing when applied to in vivo implantation and regeneration. [9][10][11][12][13][14] In terms of NGC fabrication, biomaterial selection and optimization are also important for an ultimately good nerve regeneration outcome.…”

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confidence: 99%

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Evaluation of Small Intestine Submucosa and Poly(caprolactone-co-lactide) Conduits for Peripheral Nerve Regeneration

Shim

Kwon

Lee

et al. 2015

Tissue Engineering Part A

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The present study employed nerve guidance conduits (NGCs) only, which were made of small intestine submucosa (SIS) and poly(caprolactone-co-lactide) (PCLA) to promote nerve regeneration in a peripheral nerve injury (PNI) model with nerve defects of 15 mm. The SIS-and PCLA-NGCs were easily prepared by rolling of a SIS sheet and a bioplotter using PCLA, respectively. The prepared SIS-and PCLA-NGCs fulfilled the general requirement for use as artificial peripheral NGCs such as easy fabrication, reproducibility for mass production, suturability, sterilizability, wettability, and proper mechanical properties to resist collapsing when applied to in vivo implantation. The SIS-and PCLA-NGCs appeared to be well integrated into the host sciatic nerve without causing dislocations and serious inflammation. All NGCs stably maintained their NGC shape for 8 weeks without collapsing, which matched well with the nerve regeneration rate. Staining of the NGCs in the longitudinal direction showed that the regenerated nerves grew successfully from the SIS-and PCLA-NGCs through the sciatic nerve-injured gap and connected from the proximal to distal direction along the NGC axis. SIS-NGCs exhibited a higher nerve regeneration rate than PCLANGCs. Collectively, our results indicate that SIS-and PCLA-NGCs induced nerve regeneration in a PNI model, a finding that has significant implications in the future with regard to the feasibility of clinical nerve regeneration with SIS-and PCLA-NGCs prepared through an easy fabrication method using promising biomaterials.

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confidence: 99%

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confidence: 99%

Evaluation of Small Intestine Submucosa and Poly(caprolactone-co-lactide) Conduits for Peripheral Nerve Regeneration

Shim

Kwon

Lee

et al. 2015

Tissue Engineering Part A

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“…Effectively bridging the rostral and caudal stumps has been one of the top priorities for spinal cord repair [46,55,56] . In this study, we employed a multichannel PLGA scaffold seeded with ASCs and MSCs to bridge the lesion gap after complete transection of the thoracic spinal cord in adult rats.…”

Section: Discussionmentioning

confidence: 99%

Multichannel polymer scaffold seeded with activated Schwann cells and bone mesenchymal stem cells improves axonal regeneration and functional recovery after rat spinal cord injury

Yang

Zhang

et al. 2017

Acta Pharmacol Sin

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The adult mammalian CNS has a limited capacity to regenerate after traumatic injury. In this study, a combinatorial strategy to promote axonal regeneration and functional recovery after spinal cord injury (SCI) was evaluated in adult rats. The rats were subjected to a complete transection in the thoracic spinal cord, and multichannel scaffolds seeded with activated Schwann cells (ASCs) and/or rat bone marrow-derived mesenchymal stem cells (MSCs) were acutely grafted into the 3-mm-wide transection gap. At 4 weeks posttransplantation and thereafter, the rats receiving scaffolds seeded with ASCs and MSCs exhibited significant recovery of nerve function as shown by the Basso, Beattie and Bresnahan (BBB) score and electrophysiological test results. Immunohistochemical analyses at 4 and 8 weeks after transplantation revealed that the implanted MSCs at the lesion/graft site survived and differentiated into neuron-like cells and co-localized with host neurons. Robust bundles of regenerated fibers were identified in the lesion/graft site in the ASC and MSC co-transplantation rats, and neurofilament 200 (NF) staining confirmed that these fibers were axons. Furthermore, myelin basic protein (MBP)-positive myelin sheaths were also identified at the lesion/graft site and confirmed via electron microscopy. In addition to expressing mature neuronal markers, sparse MSC-derived neuron-like cells expressed choline acetyltransferase (ChAT) at the injury site of the ASC and MSC co-transplantation rats. These findings suggest that co-transplantation of ASCs and MSCs in a multichannel polymer scaffold may represent a novel combinatorial strategy for the treatment of spinal cord injury.

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“…This suggests that MSCs may affect cell regeneration and repair, through control of apoptosis following SCI [63].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Bone Marrow Derived Mesenchymal Stem Cells in Modulating Astroglyosis of Surgical Induced Experimental Spinal Cord Injury

Elawady¹,

Elmaghrabi²,

Ebrahim³

et al. 2016

ABB

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Background: Spinal cord injury (SCI) unsuccessful regeneration was due to glial scar development. It was a major obstacle to axonal restoration. Safe therapeutic intervention by the use of bone marrow derived stem cells (BMMSCs) transplantation applied in the present study could reduce spinal disability. Material and methods: Forty male albino rats were divided into four groups: GI: negative control (n = 10 rats); GII: positive control after SCI (n = 10 rats); GIII: SCI + BM − MSCs intravenous injected and GIV: SCI + BM − MSCs intra lesion injected (n = 10 rats in each group). The samples were taken from spinal cord tissues around the region of injury and were subjected to histological, immunohistochemical assessment. RNA extraction and real time PCR for detection of nerve regeneration and astrocyte response to the injury were also performed. Results: Clinical improvement occurred by the enhancement in the Basso, Beattie and Bresnahan (BBB) score after SCI. Histological examinations showed positive regenerative responses in GIV compared to GIII. Conclusion: BM-MSCs transplantation has a promising role in enhancing the microenvironment for nerve regeneration through stumbling the glial scaring formation and inflammatory response after chronic spinal cord injury especially by using intra-lesion route injection.

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Tissue engineered regeneration of completely transected spinal cord using human mesenchymal stem cells

Cited by 56 publications

References 45 publications

Evaluation of Small Intestine Submucosa and Poly(caprolactone-co-lactide) Conduits for Peripheral Nerve Regeneration

Evaluation of Small Intestine Submucosa and Poly(caprolactone-co-lactide) Conduits for Peripheral Nerve Regeneration

Multichannel polymer scaffold seeded with activated Schwann cells and bone mesenchymal stem cells improves axonal regeneration and functional recovery after rat spinal cord injury

Therapeutic Potential of Bone Marrow Derived Mesenchymal Stem Cells in Modulating Astroglyosis of Surgical Induced Experimental Spinal Cord Injury

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