Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury

Cheng, Hao‐Tsai; Liu, Xuebin; Hua, Rongrong; Dai, Guohao; Xiao-dong, Wang; Gao, Jianhua; An, Yu

doi:10.1186/s12967-014-0253-7

Cited by 126 publications

(76 citation statements)

References 23 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The hWJ-MSCs currently represent a promising cell type in regenerative medicine and are already being evaluated in various clinical trials, including SCI. 30 The in vitro 2D cell culture demonstrated that both types of ECM hydrogels promoted adhesion and proliferation of hWJ-MSCs.…”

Section: Discussionmentioning

confidence: 97%

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair

Tukmachev

Forostyak

Kočí

et al. 2016

Tissue Engineering Part A

139

107

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 97%

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair

Tukmachev

Forostyak

Kočí

et al. 2016

Tissue Engineering Part A

139

107

View full text Add to dashboard Cite

show abstract

“…MSCs transplantations via different routes of administration have been widely studied in different species of SCI (spinal cord injury), and have been proven to produce beneficial effects following SCI (Table ). The systemic or intraspinal cord administration of MSCs significantly attenuates SCI in rodents (Chopp et al., ; Hu et al., ; Kao, Chen, Chio, & Lin, ; Lu, Jones, & Tuszynski, ; Okano et al., ; Satake, Lou, & Lenke, ), dogs (Penha et al., ), rabbits (Moon et al., ), monkeys (Deng et al., ), or patients (Arien‐Zakay et al., ; Cheng et al., ; Jiang et al., ; Mendonça et al., ). MSCs are beneficial in reversing the neurological motor deficits of SCI, even when infused 5 days after injury (Saporta et al., ).…”

Section: Therapy With Conditioned Medium From Cultured Mscs Improves mentioning

confidence: 99%

Mesenchymal stem cell‐based treatments for stroke, neural trauma, and heat stroke

et al. 2016

View full text Add to dashboard Cite

BackgroundMesenchymal stem cell (MSC) transplantation has been reported to improve neurological function following neural injury. Many physiological and molecular mechanisms involving MSC therapy‐related neuroprotection have been identified.MethodsA review is presented of articles that pertain to MSC therapy and diverse brain injuries including stroke, neural trauma, and heat stroke, which were identified using an electronic search (e.g., PubMed), emphasize mechanisms of MSC therapy‐related neuroprotection. We aim to discuss neuroprotective mechanisms that underlie the beneficial effects of MSCs in treating stroke, neural trauma, and heatstroke.Results MSC therapy is promising as a means of augmenting brain repair. Cell incorporation into the injured tissue is not a prerequisite for the beneficial effects exerted by MSCs. Paracrine signaling is believed to be the most important mediator of MSC therapy in brain injury. The multiple mechanisms of action of MSCs include enhanced angiogenesis and neurogenesis, immunomodulation, and anti‐inflammatory effects. Microglia are the first source of the inflammatory cascade during brain injury. Cytokines, including tumor necrosis factor‐α, interleukin‐1β, and interleukin‐6, are significantly produced by microglia in the brain after experimental brain injury. The proinflammatory M1 phenotype of microglia is associated with tissue destruction, whereas the anti‐inflammatory M2 phenotype of microglia facilitates repair and regeneration. MSC therapy may improve outcomes of ischemic stroke, neural trauma, and heatstroke by inhibiting the activity of M1 phenotype of microglia but augmenting the activity of M2 phenotype of microglia.ConclusionThis review offers a testable platform for targeting microglial‐mediated cytokines in clinical trials based upon the rational design of MSC therapy in the future. MSCs that are derived from the placenta provide a great choice for stem cell therapy. Although targeting the microglial activation is an important approach to reduce the burden of the injury, it is not the only one. This review focuses on this specific aspect.

show abstract

“…We used hWJ‐MSCs, as these cells represent an easily accessible source, with high potential for clinical applications. Moreover, a therapeutic benefit of hWJ‐MSCs in SCI alone as well as in combination with a biomaterial has been shown previously in several experimental and clinical studies …”

Section: Introductionmentioning

confidence: 52%

“…Moreover, a therapeutic benefit of hWJ-MSCs in SCI alone as well as in combination with a biomaterial has been shown previously in several experimental and clinical studies. [35][36][37]…”

Section: Introductionmentioning

confidence: 99%

Injectable hydroxyphenyl derivative of hyaluronic acid hydrogel modified with RGD as scaffold for spinal cord injury repair

Zaviskova

Tukmachev

Dubisova

et al. 2018

J Biomedical Materials Res

View full text Add to dashboard Cite

Hydrogel scaffolds which bridge the lesion, together with stem cell therapy represent a promising approach for spinal cord injury (SCI) repair. In this study, a hydroxyphenyl derivative of hyaluronic acid (HA-PH) was modified with the integrin-binding peptide arginine-glycine-aspartic acid (RGD), and enzymatically crosslinked to obtain a soft injectable hydrogel. Moreover, addition of fibrinogen was used to enhance proliferation of human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) on HA-PH-RGD hydrogel. The neuroregenerative potential of HA-PH-RGD hydrogel was evaluated in vivo in acute and subacute models of SCI. Both HA-PH-RGD hydrogel injection and implantation into the acute spinal cord hemisection cavity resulted in the same axonal and blood vessel density in the lesion area after 2 and 8 weeks. HA-PH-RGD hydrogel alone or combined with fibrinogen (HA-PH-RGD/F) and seeded with hWJ-MSCs was then injected into subacute SCI and evaluated after 8 weeks using behavioural, histological and gene expression analysis. A subacute injection of both HA-PH-RGD and HA-PH-RGD/F hydrogels similarly promoted axonal ingrowth into the lesion and this effect was further enhanced when the HA-PH-RGD/F was combined with hWJ-MSCs. On the other hand, no effect was found on locomotor recovery or the blood vessel ingrowth and density of glial scar around the lesion. In conclusion, we have developed and characterized injectable HA-PH-RGD based hydrogel, which represents a suitable material for further combinatorial therapies in neural tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1129-1140, 2018.

show abstract

Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury

Cited by 126 publications

References 23 publications

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair

Mesenchymal stem cell‐based treatments for stroke, neural trauma, and heat stroke

Injectable hydroxyphenyl derivative of hyaluronic acid hydrogel modified with RGD as scaffold for spinal cord injury repair

Contact Info

Product

Resources

About