Neural progenitor diversity and their therapeutic potential for spinal cord repair

Mesenchymal stromal cells (MSC) are used for cell therapy for spinal cord injury (SCI) because of their ability to support tissue repair by paracrine signaling. Preclinical and clinical research testing MSC transplants for SCI have revealed limited success, which warrants the exploration of strategies to improve their therapeutic efficacy. MSC are sensitive to the microenvironment and their secretome can be altered in vitro by exposure to different culture media. Priming MSC with inflammatory stimuli increases the expression and secretion of reparative molecules. We studied the effect of macrophage-derived inflammation priming on MSC transplants and of primed MSC (pMSC) acute transplants (3 days) on spinal cord repair using an adult rat model of moderate–severe contusive SCI. We found a decrease in long-term survival of pMSC transplants compared with unprimed MSC transplants. With a pMSC transplant, we found significantly more anti-inflammatory macrophages in the contusion at 4 weeks post transplantation (wpt). Blood vessel presence and maturation in the contusion at 1 wpt was similar in rats that received pMSC or untreated MSC. Nervous tissue sparing and functional recovery were similar across groups. Our results indicate that macrophage-derived inflammation priming does not increase the overall therapeutic potential of an MSC transplant in the adult rat contused spinal cord.

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Exercise may speed spinal cord repair

Nature ◽

10.1038/news031110-2 ◽

2003 ◽

Cited By ~ 2

Author(s):

Helen R. Pilcher

Keyword(s):

Spinal Cord ◽

Spinal Cord Repair

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Stem Cell Transplantation: A Promising Therapy for Spinal Cord Injury

Current Stem Cell Research & Therapy ◽

10.2174/1574888x14666190823144424 ◽

2020 ◽

Vol 15 (4) ◽

pp. 321-331 ◽

Cited By ~ 2

Author(s):

Zhe Gong ◽

Kaishun Xia ◽

Ankai Xu ◽

Chao Yu ◽

Chenggui Wang ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Therapeutic Potential ◽

Embryonic Stem ◽

Current Status ◽

Cord Injury

Spinal Cord Injury (SCI) causes irreversible functional loss of the affected population. The incidence of SCI keeps increasing, resulting in huge burden on the society. The pathogenesis of SCI involves neuron death and exotic reaction, which could impede neuron regeneration. In clinic, the limited regenerative capacity of endogenous cells after SCI is a major problem. Recent studies have demonstrated that a variety of stem cells such as induced Pluripotent Stem Cells (iPSCs), Embryonic Stem Cells (ESCs), Mesenchymal Stem Cells (MSCs) and Neural Progenitor Cells (NPCs) /Neural Stem Cells (NSCs) have therapeutic potential for SCI. However, the efficacy and safety of these stem cellbased therapy for SCI remain controversial. In this review, we introduce the pathogenesis of SCI, summarize the current status of the application of these stem cells in SCI repair, and discuss possible mechanisms responsible for functional recovery of SCI after stem cell transplantation. Finally, we highlight several areas for further exploitation of stem cells as a promising regenerative therapy of SCI.

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Inhibition of Glycine Re-Uptake: A Potential Approach for Treating Pain by Augmenting Glycine-Mediated Spinal Neurotransmission and Blunting Central Nociceptive Signaling

Biomolecules ◽

10.3390/biom11060864 ◽

2021 ◽

Vol 11 (6) ◽

pp. 864

Author(s):

Christopher L. Cioffi

Keyword(s):

Spinal Cord ◽

Dorsal Horn ◽

Therapeutic Potential ◽

Opioid Analgesic ◽

Critical Role ◽

Analgesic Efficacy ◽

Standard Of Care ◽

Current Standard ◽

Glycine Transporters ◽

Pathological Pain

Among the myriad of cellular and molecular processes identified as contributing to pathological pain, disinhibition of spinal cord nociceptive signaling to higher cortical centers plays a critical role. Importantly, evidence suggests that impaired glycinergic neurotransmission develops in the dorsal horn of the spinal cord in inflammatory and neuropathic pain models and is a key maladaptive mechanism causing mechanical hyperalgesia and allodynia. Thus, it has been hypothesized that pharmacological agents capable of augmenting glycinergic tone within the dorsal horn may be able to blunt or block aberrant nociceptor signaling to the brain and serve as a novel class of analgesics for various pathological pain states. Indeed, drugs that enhance dysfunctional glycinergic transmission, and in particular inhibitors of the glycine transporters (GlyT1 and GlyT2), are generating widespread interest as a potential class of novel analgesics. The GlyTs are Na+/Cl−-dependent transporters of the solute carrier 6 (SLC6) family and it has been proposed that the inhibition of them presents a possible mechanism by which to increase spinal extracellular glycine concentrations and enhance GlyR-mediated inhibitory neurotransmission in the dorsal horn. Various inhibitors of both GlyT1 and GlyT2 have demonstrated broad analgesic efficacy in several preclinical models of acute and chronic pain, providing promise for the approach to deliver a first-in-class non-opioid analgesic with a mechanism of action differentiated from current standard of care. This review will highlight the therapeutic potential of GlyT inhibitors as a novel class of analgesics, present recent advances reported for the field, and discuss the key challenges associated with the development of a GlyT inhibitor into a safe and effective agent to treat pain.

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CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis

Scientific Reports ◽

10.1038/s41598-021-93232-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Daekwon Bae ◽

Ji-Young Lee ◽

Nina Ha ◽

Jinsol Park ◽

Jiyeon Baek ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Immune Responses ◽

Therapeutic Potential ◽

Autoimmune Encephalitis ◽

Selective Inhibitor ◽

Therapeutic Effects ◽

Treatment Regimens ◽

Ifn Γ ◽

Experimental Autoimmune

AbstractDespite advances in therapeutic strategies for multiple sclerosis (MS), the therapy options remain limited with various adverse effects. Here, the therapeutic potential of CKD-506, a novel HDAC6-selective inhibitor, against MS was evaluated in mice with myelin oligodendrocyte glycoprotein35–55 (MOG35–55)-induced experimental autoimmune encephalitis (EAE) under various treatment regimens. CKD-506 exerted prophylactic and therapeutic effects by regulating peripheral immune responses and maintaining blood–brain barrier (BBB) integrity. In MOG35–55-re-stimulated splenocytes, CKD-506 decreased proliferation and downregulated the expression of IFN-γ and IL-17A. CKD-506 downregulated the levels of pro-inflammatory cytokines in the blood of EAE mice. Additionally, CKD-506 decreased the leakage of intravenously administered Evans blue into the spinal cord; CD4+ T cells and CD4−CD11b+CD45+ macrophage/microglia in the spinal cord was also decreased. Moreover, CKD-506 exhibited therapeutic efficacy against MS, even when drug administration was discontinued from day 15 post-EAE induction. Disease exacerbation was not observed when fingolimod was changed to CKD-506 from day 15 post-EAE induction. CKD-506 alleviated depression-like behavior at the pre-symptomatic stage of EAE. In conclusion, CKD-506 exerts therapeutic effects by regulating T cell- and macrophage-mediated peripheral immune responses and strengthening BBB integrity. Our results suggest that CKD-506 is a potential therapeutic agent for MS.

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Successful application of burst spinal cord stimulation for refractory upper limb pain: a case series

Journal of International Medical Research ◽

10.1177/03000605211004035 ◽

2021 ◽

Vol 49 (3) ◽

pp. 030006052110040

Author(s):

Kuen Su Lee ◽

Yoo Kyung Jang ◽

Gene Hyun Park ◽

In Jae Jun ◽

Jae Chul Koh

Keyword(s):

Spinal Cord ◽

Upper Limb ◽

Spinal Cord Stimulation ◽

Therapeutic Potential ◽

Case Series ◽

Limb Amputation ◽

Intractable Pain ◽

Limb Pain ◽

Cord Injury ◽

Upper Limb Pain

Spinal cord stimulation (SCS) has been used to treat sustained pain that is intractable despite various types of treatment. However, conventional tonic waveform SCS has not shown promising outcomes for spinal cord injury (SCI) or postamputation pain. The pain signal mechanisms of burst waveforms are different to those of conventional tonic waveforms, but few reports have presented the therapeutic potential of burst waveforms for the abovementioned indications. This current case report describes two patients with refractory upper limb pain after SCI and upper limb amputation that were treated with burst waveform SCS. While the patients could not obtain sufficient therapeutic effect with conventional tonic waveforms, the burst waveforms provided better pain reduction with less discomfort. However, further studies are necessary to better clarify the mechanisms and efficacy of burst waveform SCS in patients with intractable pain.

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