This study is aimed at describing a novel method for treating patients with chronic complete spinal cord injuries (SCIs) by utilizing autologous, purified CD34 + and CD133 + stem cells (SCs). The study focuses on the safety and efficacy of transplanting unmanipulated, autologous, purified stem cells in treated patients during a 5-year follow-up period. In this report, 19 patients were included (16 males and 3 females) who presented with a complete SCI (ASIA-A) in the thoracic region. The patients' endogenous cells were mobilized with subcutaneous granulocyte-colony-stimulating factor (G-CSF) for 5 days. We utilized the CliniMACS magnetic separation system to purify leukapheresis-derived CD34 + and CD133 + SCs. Purified SCs were directly transplanted into the SCI site. Patients were then monitored and followed for up to 5 years. On average, 76 × 10 6 purified SCs were obtained from each patient, with 95.2% purity and >98% viability. SC transplantation into the cyst cavity or the subarachnoid space was successful and well tolerated in all 19 patients and did not cause any allergic or inflammatory reactions within the CNS in the early or late periods after transplantation. Ten patients (53%) showed no improvement after 42-60 months (ASIA-A), while seven patients (37%) demonstrated segmental sensory improvement (ASIA-B), and the remaining two patients (10%) had motor improvement (ASIA-C). This study presents a safe method for transplanting specific populations of purified autologous SCs that can be used to treat SCIs in a clinical setting. The results may be utilized as a stepping-stone for future investigations in the field of regenerative medicine for treatment of SCIs and other neurological diseases. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.
Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version “Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)”. The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.
Background:Methods to obtain safe and practical populations of stem cells (SCs) at a clinical grade that are able to differentiate into neuronal cell lineages are yet to be developed. In a previous study, we showed that mouse bone marrow-derived SCs (BM-SCs) differentiated into neuronal cell-like lineages when put in a neuronal-like environment, which is a special media supplemented with the necessary growth factors needed for the differentiation of SCs into neuronal cell-like lineages. Aim: In this study, we aim to assess the potentials of adult human CD34+ and CD133+ SCs to differentiate into neuronal cell-like lineages ex vivo when placed in a neuronal-like microenvironment. Methods: The neuronal-like microenvironment was created by culturing cells in nonhematopoietic expansion media (NHEM) supplemented with growth factors that favor differentiation into neuronal cell lineages (low-affinity nerve growth factor [LNGF], mouse spinal cord extract [mSpE], or both). Cultured cells were assessed for neuronal differentiation by cell morphologies and by expression of GFAP. Results: Our results show that culturing unpurified human BM-derived mononuclear cells (hBM-MNCs) in NHEM+LNGF+mSpE did not lead to neuronal differentiation. In contrast, culturing of purified CD34+ hBM-SCs in NHEM+LNGF+mSpE favored their differentiation into astrocyte-like cells, whereas culturing of purified CD133+ hBM-SCs in the same media favored their differentiation into neuronal-like cells. Interestingly, coculturing of CD34+ and CD133+ hBM-SCs in the same media enhanced the differentiation into astrocyte-like cells and neuronal-like cells, in addition to oligodendrocyte-like cells. Conclusion: These results suggest that a mixture of purified CD34+ and CD133+ cells may enhance the differentiation into neuronal cell-like lineages and give broader neuronal cell lineages than when each of these cell types is cultured alone. This method opens the window for the utilization of specific populations of hBM-SCs to be delivered in a purified form for the potential treatment of neurodegenerative diseases in the future.
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