At present, Spinal cord injury stem cell therapy is a therapeutic promise in this field of research 1) 2) 3) 4) 5) 6) 7) 8) 9) but still subject to many uncertainties, with significant confusion due to the disparity of protocols, selection of subjects, cell type, dose and routes of administration used. In experimental studies, it is noteworthy that the functional recovery of paraplegic animals after mesenchymal stem cell (MSC) transplantation starts before tissue regeneration occurs to allow the passage of ascending and descending axons. Therefore, it is obvious that after MSC transplantation into injured central nervous system (CNS) must exist various repair processes, including the release of neurotrophic factors by the transplanted stem cells, or the activation of endogenous processes, including the release of neurotrophic factors by the transplanted stem cells, or the activation of endogenous mechanisms of the spinal cord, able to partially restore neurological functions previously abolished 10) 11) 12) 13) 14) 15) 16) 17) 18).

Unflammation and toxins released by damaged cells at the site of a spinal injury often cause further harm to surrounding cells. Researchers are developing treatments that reduce inflammation and soak up toxins and free radicals to minimise additional damage.

Spinal cord injuries often damage neurons and the supporting cells that wrap & insulate neurons. Damaging the supporting cells can cause otherwise functional neurons to die. Researchers are studying how stem cells might be used to replace neurons and their supporting cells to greatly improve a patient’s chances for recovering function.

A multi-center team is currently planning to launch a first-in-human clinical study of an induced pluripotent stem cell (iPSC)-based cell transplant intervention for subacute SCI. This trial will be conducted as Class I regenerative medicine protocol as provided for under Japan's Act on the Safety of Regenerative Medicine (ASRM), using neural stem/progenitor cells derived from a clinical-grade, integration-free human “iPSC stock” generated by the Kyoto University Center for iPS Cell Research and Application (CiRA). In a article, Tsuji et al. described how they are preparing to initiate this clinical study, including addressing the issues of safety and tumorigenesis as well as practical problems that must be overcome to enable the development of therapeutic interventions for patients with chronic SCI 19).

As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural stem cells to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NSCs before transplantation are top priorities to overcome.

Liu et al., developed a safe and cost-effective pipeline to generate clinically relevant NSCs. They first isolated cells from patients' urine and reprogrammed them into iPSCs by non-integrating Sendai virus vectors, and carried out experiments on neural differentiation. NSCs were purified by A2B5, an antibody specifically recognizing a glycoganglioside on the cell surface of neural lineage cells, via fluorescence activated cell sorting. Upon further in vitro induction, NSCs were able to give rise to neurons, oligodendrocytes and astrocytes. To test the functionality of the A2B5+ NSCs, they grafted them into the contused mouse thoracic spinal cord. Eight weeks after transplantation, the grafted cells survived, integrated into the injured spinal cord, and differentiated into neurons and glia.

The specific focus on cell source, reprogramming, differentiation and purification method purposely addresses timing and safety issues of transplantation to SCI models. It is Liu et al., belief that this work takes one step closer on using human iPSC derivatives to SCI clinical settings 20).

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Tsuji O, Sugai K, Yamaguchi R, Tashiro S, Nagoshi N, Kohyama J, Iida T, Ohkubo T, Itakura G, Isoda M, Shinozaki M, Fujiyoshi K, Kanemura Y, Yamanaka S, Nakamura M, Okano H. Laying the groundwork for a first-in-human study of an iPSC-based intervention for spinal cord injury. Stem Cells. 2018 Oct 29. doi: 10.1002/stem.2926. [Epub ahead of print] Review. PubMed PMID: 30371964.
Liu Y, Zheng Y, Li S, Xue H, Schmitt K, Hergenroeder GW, Wu J, Zhang Y, Kim DH, Cao Q. Human neural progenitors derived from integration-free iPSCs for SCI therapy. Stem Cell Res. 2017 Jan 5;19:55-64. doi: 10.1016/j.scr.2017.01.004. [Epub ahead of print] PubMed PMID: 28073086.
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