Cellular therapies for treating pain associated with spinal cord injury

Leung, Lawrence C.

doi:10.1186/1479-5876-10-37

Cited by 9 publications

(9 citation statements)

References 168 publications

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“…A principal finding in this study was that probiotic or ADMSC treatment notably and comparably preserved the functional integrity of peripheral nerves, i.e., upregulated the hyperalgesia threshold, resulting in augmentation of the analgesia of NP. In this way, our finding reinforced the findings of previous research [ 24 , 48 , 49 ]. Of innovative finding in the present study was that combination treatment with probiotics and ADMSCs could even offer a synergic effect on upregulating the thresholds of TPWL and MPWT (i.e., indicated by the pain threshold that was defined as the point beyond which a stimulus caused pain), suggesting that our findings extended the findings of previous investigations [ 24 , 48 , 49 ].…”

Section: Discussionsupporting

confidence: 93%

“…In this way, our finding reinforced the findings of previous research [ 24 , 48 , 49 ]. Of innovative finding in the present study was that combination treatment with probiotics and ADMSCs could even offer a synergic effect on upregulating the thresholds of TPWL and MPWT (i.e., indicated by the pain threshold that was defined as the point beyond which a stimulus caused pain), suggesting that our findings extended the findings of previous investigations [ 24 , 48 , 49 ].…”

Section: Discussionsupporting

confidence: 93%

“…Only limited studies have previously reported that cell-based therapy could serve as an innovative therapy for painful peripheral neuropathy [ 48 , 49 ]. On the other hand, fewer studies have revealed that probiotic therapy would act as a possible adjuvant regimen for counteracting NP [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

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Synergic Effect of Early Administration of Probiotics and Adipose-Derived Mesenchymal Stem Cells on Alleviating Inflammation-Induced Chronic Neuropathic Pain in Rodents

Chen

Lin

et al. 2022

IJMS

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This study investigated the hypothesis that probiotics enhanced the therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) on alleviating neuropathic pain (NP) due to chronic constriction injury (CCI) mainly through regulating the microbiota in rats. SD rats (n = 50) were categorized into group 1 (sham-control), group 2 (NP), group 3 (NP + probiotics (i.e., 1.5 billion C.F.U./day/rat, orally 3 h after NP procedure, followed by QOD 30 times)), group 4 (NP + ADMSCs (3.0 × 105 cells) 3 h after CCI procedure, followed by QOD six times (i.e., seven times in total, i.e., mimic a clinical setting of drug use) and group 5 (NP + probiotics + ADMSCs (3.0 × 105 cells)) and euthanized by day 60 after NP induction. By day 28 after NP induction, flow-cytometric analysis showed circulating levels of early (AN-V+/PI−) and late (AN-V+/PI+) apoptotic, and three inflammatory (CD11b-c+, Ly6G+ and MPO+) cells were lowest in group 1 and significantly progressively reduced in groups 2 to 5 (all p < 0.0001). By days 7, 14, 21, 28, and 60 after CCI, the thresholds of thermal paw withdrawal latency (PWL) and mechanical paw withdrawal threshold (PWT) were highest in group 1 and significantly progressively increased in groups 2 to 5 (all p < 0.0001). Numbers of pain-connived cells (Nav1.8+/peripherin+, p-ERK+/peripherin+, p-p38+/peripherin+ and p-p38+/NF200+) and protein expressions of inflammatory (p-NF-κB, IL-1ß, TNF-α and MMP-9), apoptotic (cleaved-caspase-3, cleaved-PARP), oxidative-stress (NOX-1, NOX-2), DNA-damaged (γ-H2AX) and MAPK-family (p-P38, p-JNK, p-ERK1/2) biomarkers as well as the protein levels of Nav.1.3, Nav.1.8, and Nav.1.9 in L4-L5 in dorsal root ganglia displayed an opposite pattern of mechanical PWT among the groups (all p < 0.0001). In conclusion, combined probiotic and ADMSC therapy was superior to merely one for alleviating CCI-induced NP mainly through suppressing inflammation and oxidative stress.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

Synergic Effect of Early Administration of Probiotics and Adipose-Derived Mesenchymal Stem Cells on Alleviating Inflammation-Induced Chronic Neuropathic Pain in Rodents

Chen

Lin

et al. 2022

IJMS

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“…Cell-based therapy has been proposed as a novel approach for treating painful peripheral neuropathy [1,2]. Transplantation of mesenchymal stem cells (MSCs) has been demonstrated to be a potentially therapeutic approach for the alleviation of chronic pain from various etiologies [2][3][4][5][6][7][8]. Prior studies have reported pain relief in rodent chronic pain models using systemic administration of MSCs [4,8], but this delivery approach requires large preparations of transplantable cells, depends on a nebulously defined propensity of MSCs to home in on injured tissue, and leads to MSCs trapping in the lung, liver, resulting in off-site tissue damage [9,10], making targeted delivery preferable.…”

Section: Introductionmentioning

confidence: 99%

Analgesia for Neuropathic Pain by Dorsal Root Ganglion Transplantation of Genetically Engineered Mesenchymal Stem Cells: Initial Results

Fischer

Ebert

et al. 2015

Mol Pain

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BackgroundCell-based therapy may hold promise for treatment of chronic pain. Mesenchymal stem cells (MSCs) are readily available and robust, and their secretion of therapeutic peptides can be enhanced by genetically engineering. We explored the analgesic potential of transplanting bone marrow-derived MSCs that have been transduced with lentivectors. To optimize efficacy and safety, primary sensory neurons were targeted by MSC injection into the dorsal root ganglia (DRGs).ResultsMSCs were transduced using lentivectors to express enhanced green fluorescent protein (EGFP) or to co-express the analgesic peptide glial cell line-derived neurotrophic factor (GDNF) and EGFP by a viral 2A bicistronic transgene cassette. Engineered MSCs were injected into the 4th lumbar (L4) and L5 DRGs of adult allogeneic rats to evaluate survival in the DRGs. MSCs were detected by immunofluorescence staining up to 2–3 weeks after injection, distributed in the extracellular matrix space without disrupting satellite glial cell apposition to sensory neurons, suggesting well-tolerated integration of engrafted MSCs into DRG tissue. To examine their potential for inhibiting development of neuropathic pain, MSCs were injected into the L4 and L5 DRGs ipsilateral to a spinal nerve ligation injury. Animals injected with GDNF-engineered MSCs showed moderate but significant reduction in mechanical allodynia and hyperalgesia compared to controls implanted with MSCs expressing EGFP alone. We also observed diminished long-term survival of allografted MSCs at 3 weeks, and the development of a highly-proliferating population of MSCs in 12% of DRGs after transplantation.ConclusionsThese data indicate that genetically modified MSCs secreting analgesic peptides could potentially be developed as a novel DRG-targeted cell therapy for treating neuropathic pain. However, further work is needed to address the challenges of MSC survival and excess proliferation, possibly with trials of autologous MSCs, evaluation of clonally selected populations of MSCs, and investigation of regulation of MSC proliferation.

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“…New advances from preclinical and clinical studies offer potential neuroprotective and therapeutic possibilities 3 , 4 ; however, due to the poor intrinsic regenerative capability of the spinal cord, treatment of SCI is still a significant problem. A major challenge in repairing the injured spinal cord is how to regenerate tissue and encourage regrowth of severed axons with cellular and molecular therapies 5 , 6 , although several growth factors have been applied for the treatment of SCI 6 .…”

Section: Introductionmentioning

confidence: 99%

Collagen-Binding Hepatocyte Growth Factor (HGF) alone or with a Gelatin- furfurylamine Hydrogel Enhances Functional Recovery in Mice after Spinal Cord Injury

Yamane

Mazaki

Sugiyama

et al. 2018

Sci Rep

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The treatment of spinal cord injury (SCI) is currently a significant challenge. Hepatocyte growth factor (HGF) is a multipotent neurotrophic and neuroregenerative factor that can be beneficial for the treatment of SCI. However, immobilized HGF targeted to extracellular matrix may be more effective than diffusible, unmodified HGF. In this study, we evaluated the neurorestorative effects of an engineered HGF with a collagen biding domain (CBD-HGF). CBD-HGF remained in the spinal cord for 7 days after a single administration, while unmodified HGF was barely seen at 1 day. When a gelatin-furfurylamine (FA) hydrogel was applied on damaged spinal cord as a scaffold, CBD-HGF was retained in gelatin-FA hydrogel for 7 days, whereas HGF had faded by 1 day. A single administration of CBD-HGF enhanced recovery from spinal cord compression injury compared with HGF, as determined by motor recovery, and electrophysiological and immunohistochemical analyses. CBD-HGF alone failed to improve recovery from a complete transection injury, however CBD-HGF combined with gelatin-FA hydrogel promoted endogenous repair and recovery more effectively than HGF with hydrogel. These results suggest that engineered CBD-HGF has superior therapeutic effects than naïve HGF. CBD-HGF combined with hydrogel scaffold may be promising for the treatment of serious SCI.

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Cellular therapies for treating pain associated with spinal cord injury

Cited by 9 publications

References 168 publications

Synergic Effect of Early Administration of Probiotics and Adipose-Derived Mesenchymal Stem Cells on Alleviating Inflammation-Induced Chronic Neuropathic Pain in Rodents

Synergic Effect of Early Administration of Probiotics and Adipose-Derived Mesenchymal Stem Cells on Alleviating Inflammation-Induced Chronic Neuropathic Pain in Rodents

Analgesia for Neuropathic Pain by Dorsal Root Ganglion Transplantation of Genetically Engineered Mesenchymal Stem Cells: Initial Results

Collagen-Binding Hepatocyte Growth Factor (HGF) alone or with a Gelatin- furfurylamine Hydrogel Enhances Functional Recovery in Mice after Spinal Cord Injury

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