Safety and efficiency of Wharton's Jelly-derived mesenchymal stem cell administration in patients with traumatic brain injury: First results of a phase I study.

BACKGROUND: Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. Stem cell transplantation has evolved as a novel treatment modality in the management of TBI, as it has the potential to arrest the degeneration and promote regeneration of new cells in the brain. Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) have recently shown beneficial effects in the functional recovery of neurological deficits. AIM: To evaluate the safety and efficiency of MSC therapy in TBI. METHODS: We present 6 patients, 4 male and 2 female aged between 21 and 27 years who suffered a TBI. These 6 patients underwent 6 doses of intrathecal, intramuscular (i.m.) and intravenous transplantation of WJ-MSCs at a target dose of 1 × 106/kg for each application route. Spasticity was assessed using the Modified Ashworth scale (MAS), motor function according to the Medical Research Council Muscle Strength Scale, quality of life was assessed by the Functional Independence Measure (FIM) scale and Karnofsky Performance Status scale. RESULTS: Our patients showed only early, transient complications, such as subfebrile fever, mild headache, and muscle pain due to i.m. injection, which resolved within 24 h. During the one year follow-up, no other safety issues or adverse events were reported. These 6 patients showed improvements in their cognitive abilities, muscle spasticity, muscle strength, performance scores and fine motor skills when compared before and after the intervention. MAS values, which we used to assess spasticity, were observed to statistically significantly decrease for both left and right sides (P < 0.001). The FIM scale includes both motor scores (P < 0.05) and cognitive scores (P < 0.001) and showed a significant increase in pretest posttest analyses. The difference observed in the participants' Karnofsky Performance Scale values pre and post the intervention was statistically significant (P < 0.001). CONCLUSION: This study showed that cell transplantation has a safe, effective and promising future in the management of TBI.

Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy.

BACKGROUND: Cerebral palsy (CP) describes a group of disorders affecting movement, balance, and posture. Disturbances in motor functions constitute the main body of CP symptoms. These symptoms surface in early childhood and patients are affected for the rest of their lives. Currently, treatment involves various pharmacotherapies for different types of CP, including antiepileptics for epilepsy and Botox A for focal spasticity. However, none of these methods can provide full symptom relief. This has prompted researchers to look for new treatment modalities, one of which is mesenchymal stem cell therapy (MSCT). Despite being a promising tool and offering a wide array of possibilities, mesenchymal stem cells (MSCs) still need to be investigated for their efficacy and safety. AIM: To analyze the efficacy and safety of MSCT in CP patients. METHODS: Our sample consists of four CP patients who cannot stand or walk without external support. All of these cases received allogeneic MSCT six times as 1 × 106/kg intrathecally, intravenously, and intramuscularly using umbilical cord-derived MSCs (UC-MSC). We monitored and assessed the patients pre- and post-treatment using the Wee Functional Independence Measure (WeeFIM), Gross Motor Function Classification System (GMFCS), and Manual Ability Classification Scale (MACS) instruments. We utilized the Modified Ashworth Scale (MAS) to measure spasticity. RESULTS: We found significant improvements in MAS scores after the intervention on both sides. Two months: Right χ2 = 4000, P = 0.046, left χ2 = 4000, P = 0.046; four months: Right χ2 = 4000, P = 0.046, left χ2 = 4000, P = 0.046; 12 months: Right χ2 = 4000, P = 0.046, left χ2 = 4000, P = 0.046. However, there was no significant difference in motor functions based on WeeFIM results (P > 0.05). GMFCS and MACS scores differed significantly at 12 months after the intervention (P = 0.046, P = 0.046). Finally, there was no significant change in cognitive functions (P > 0.05). CONCLUSION: In light of our findings, we believe that UC-MSC therapy has a positive effect on spasticity, and it partially improves motor functions.

Effects of exosomes from mesenchymal stem cells on functional recovery of a patient with total radial nerve injury: A pilot study.

BACKGROUND: Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses. Currently, there is a lack of effective pharmacological interventions for nerve damage, despite the existence of several small compounds, peptides, hormones, and growth factors that have been suggested as potential enhancers of neuron regeneration. Despite the objective of achieving full functional restoration by surgical intervention, the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve injuries. AIM: To examine the impact of exosomes on the process of functional recovery following a complete radial nerve damage. METHODS: A male individual, aged 24, who is right-hand dominant and an immigrant, arrived with an injury caused by a knife assault. The cut is located on the left arm, specifically below the elbow. The neurological examination and electrodiagnostic testing reveal evidence of left radial nerve damage. The sural autograft was utilized for repair, followed by the application of 1 mL of mesenchymal stem cell-derived exosome, comprising 5 billion microvesicles. This exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural pathway. The patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic testing. RESULTS: The duration of the patient's follow-up period was 180 d. An increasing Tinel's sign and sensory-motor recovery were detected even at the 10th wk following nerve grafting. Upon the conclusion of the 6-mo post-treatment period, an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the nerve. This assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon scale. The results indicated that the level of improvement in motor function was classified as M5, denoting an excellent outcome. Additionally, the level of improvement in sensory function was classified as S3+, indicating a good outcome. It is noteworthy that these assessments were conducted in the absence of physical therapy. At the 10th wk post-injury, despite the persistence of substantial axonal damage, the nerve exhibited indications of nerve re-innervation as evidenced by control electromyography (EMG). In contrast to the preceding. EMG analysis revealed a significant electrophysiological enhancement in the EMG conducted at the 6th-mo follow-up, indicating ongoing regeneration. CONCLUSION: Enhanced comprehension of the neurobiological ramifications associated with peripheral nerve damage, as well as the experimental and therapy approaches delineated in this investigation, holds the potential to catalyze future clinical progress.

Percutaneous Pain Procedures in Patients Who Underwent Lumbar Disc Herniation Surgery: Is It an Important Tool in the Management of Post-Surgical Ongoing Pain?

AIM: To evaluate the efficacy of percutaneous pain interventions in patients who previously underwent lumbar disc herniation surgery. MATERIAL AND METHODS: We retrospectively analyzed 48 patients with persistent / recurring complaints who underwent lumbar disc surgery (LDS) and were treated with percutaneous interventions. They were grouped into recurrent disc herniations (RDHs) and other discovertebral pathologies (ODVP). Moreover, patients were evaluated as those who received transforaminal injection (TFI) with facet blockage (FB) and who received both caudal injection (CI) and TFI in addition to FB. Patients were evaluated using Oswestry Disability Index (ODI) and visual analog scale (VAS). RESULTS: Between the recurrent and ODVP groups, preoperative, at 1-hour postoperative, and at 6-month postoperative ODI (p=0.867, p=0.055, p=0.892) and VAS (p=0.902, p=0.136, p=0.462) scores did not show a statistically significant difference, respectively. Additionally, in the comparison of patients who underwent FB+TFI+CI and only FB+TFI, there was no statistically significant correlation between preoperative and 6-month postoperative ODI (p = 0.284) and VAS (p=0.248) scores in both recurrent and ODVP groups, respectively. The success rates at the 3rd and 6th months of patients with RDH and ODVP were 47.61% (10/21) and 42.85% (9/21) and 70.37% (19/27) and 63.96% (17/27), respectively. CONCLUSION: There was no statistically significant difference in ODI and VAS scores between recurrent and ODVP groups. The clinical success rate was numerically better in the ODVP group. Thus, we suggest that co-administration of TFI and CI did not significantly contribute to our clinical outcome.

The Effects of Using Hearing Aids and Hearing Assistive Technologies on Programmable Ventriculoperitoneal Shunt.

BACKGROUND: To investigate interaction between behind-the-ear (BTE) hearing aids, hearing assistive technologies, and programmable shunt valve to understand how use of BTE hearing aids in patients who underwent ventriculoperitoneal shunt (VPS) surgery affects the settings of a programmable shunt valve. METHODS: In this study, we investigated the magnetic field (MF) generation of 3 BTE hearing aids made by different companies, 1 frequency modulated system using telecoil technology, and 1 wireless microphone technology and their interactions with 2 programmable shunt valves. All measurements were made in a silent booth using 2 different models. The influence of MF strength in the distance modeling was investigated based on the distance from source auditory prostheses. The measurements were recorded using a Gauss meter. In the anatomical modeling, the change in the settings and interaction of the valve in a bust mannequin were investigated. RESULTS: No MF created by BTE hearing aids was detected in the distance modeling. The highest value measured was 32.67 µT (<90 dB noise) when BTE hearing aids and frequency modulated systems were used, and this value decreased as the distance increased. No MF generation was observed at measurements done for distances >10 mm. In the anatomical modeling, the settings of both programmable valves did not change under all acoustic conditions. CONCLUSIONS: This is the first study to our knowledge examining the MF created by hearing aids and hearing assistive technologies and its impact on programmable valves and variations in their settings. Our findings showed that it is safe to use BTE hearing aids, frequency modulated systems, and wireless microphone technologies in patients with a programmable VPS.

Metric Evaluation of Reliability and Transparency of the Videos About Carpal Tunnel Syndrome Surgery in the Online Platforms: Assessment of YouTube Videos' Content.

OBJECTIVE: To evaluate the quality and reliability of carpal tunnel syndrome surgery videos on YouTube. METHODS: A keyword set of "carpal tunnel syndrome surgery" was searched on YouTube. The DISCERN scoring system, Journal of the American Medical Association (JAMA) scoring system, and Health on the Net (HON) ranking systems were used to evaluate the quality and reliability of the first 50 videos appeared in the search results. The characteristics of each video, such as the number of likes, dislikes and views, upload days, video length, and the uploader, were collected retrospectively. The relationships between the video quality and these factors were investigated statistically. RESULTS: All of the featured videos sorted were found to be of poor content (mean DISCERN score [n = 1.71 of 5], mean JAMA score [n = 1.76 of 4], mean HON score [n = 5.65 of 16]). Yet, DISCERN scores of the videos uploaded by medical centers were higher than that of the others (p = 0.022). No relationship was detected between the other variables and video quality. CONCLUSION: Healthcare professionals and organizations should be more cautious when recording and uploading a video to the online platforms. As those videos could reach a wide audience, their content should provide more information about possible complications of a treatment and other treatment modalities.

Feasibility of allogeneic mesenchymal stem cells in pediatric hypoxic-ischemic encephalopathy: Phase I study.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of death and long-term neurological impairment in the pediatric population. Despite a limited number of treatments to cure HIE, stem cell therapies appear to be a potential treatment option for brain injury resulting from HIE. AIM: To investigate the efficacy and safety of stem cell-based therapies in pediatric patients with HIE. METHODS: The study inclusion criteria were determined as the presence of substantial deficit and disability caused by HIE. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) were intrathecally (IT), intramuscularly (IM), and intravenously administered to participants at a dose of 1 × 106/kg for each administration route twice monthly for 2 mo. In different follow-up durations, the effect of WJ-MSCs administration on HIE, the quality of life, prognosis of patients, and side effects were investigated, and patients were evaluated for neurological, cognitive functions, and spasticity using the Wee Functional Independence Measure (Wee FIM) Scale and Modified Ashworth (MA) Scale. RESULTS: For all participants (n = 6), the mean duration of exposure to hypoxia was 39.17 + 18.82 min, the mean time interval after HIE was 21.83 ± 26.60 mo, the mean baseline Wee FIM scale score was 13.5 ± 0.55, and the mean baseline MA scale score was 35 ± 9.08. Three patients developed only early complications such as low-grade fever, mild headache associated with IT injection, and muscle pain associated with IM injection, all of which were transient and disappeared within 24 h. The treatment was evaluated to be safe and effective as demonstrated by magnetic resonance imaging examinations, electroencephalographies, laboratory tests, and neurological and functional scores of patients. Patients exhibited significant improvements in all neurological functions through a 12-mo follow-up. The mean Wee FIM scale score of participants increased from 13.5 ± 0.55 to 15.17 ± 1.6 points (mean ± SD) at 1 mo (z = - 1.826, P = 0.068) and to 23.5 ± 3.39 points at 12 mo (z = -2.207, P = 0.027) post-treatment. The percentage of patients who achieved an excellent functional improvement (Wee FIM scale total score = 126) increased from 10.71% (at baseline) to 12.03% at 1 mo and to 18.65% at 12 mo post-treatment. CONCLUSION: Both the triple-route and multiple WJ-MSC implantations were safe and effective in pediatric patients with HIE with significant neurological and functional improvements. The results of this study support conducting further randomized, placebo-controlled studies on this treatment in the pediatric population.

Phase I study on the safety and preliminary efficacy of allogeneic mesenchymal stem cells in hypoxic-ischemic encephalopathy.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in the adult as well as in the neonate, with limited options for treatment and significant dysfunctionality. AIM: To investigate the safety and preliminary efficacy of allogeneic mesenchymal stem cells (MSCs) in HIE patients. METHODS: Patients who had HIE for at least 6 mo along with significant dysfunction and disability were included. All patients were given Wharton's jelly-derived MSCs at 1 × 106/kg intrathecally, intravenously, and intramuscularly twice a month for two months. The therapeutic effects and prognostic implications of MSCs were evaluated by multiple follow-ups. Functional independence measure (FIM), modified Ashworth, and Karnofsky scales were used to assess any side effects, neurological and cognitive functions, and overall outcomes. RESULTS: The 8 subjects included in the study had a mean age of 33.25 ± 10.18 years. Mean HIE exposure and mean post-HIE durations were 45.63 ± 10.18 and 19.67 ± 29.04 mo, respectively. Mean FIM score was 18.38 ± 1.06, mean modified Ashworth score was 43.5 ± 4.63, and mean Karnofsky score was 20. For the first 24 h, 5 of the patients experienced a subfebrile state, accompanied by mild headaches due to intrathecally administration and muscle pain because of intramuscularly administration. Neurological and functional examinations, laboratory tests, electroencephalography, and magnetic resonance imaging were performed to assess safety of treatment. Mean FIM score increased by 20.88 ± 3.31 in the first month (P = 0.027) and by 31.38 ± 14.69 in 12 mo (P = 0.012). The rate of patients with an FIM score of 126 increased from 14.58% to 16.57% in the first month and 24.90% in 12 mo. CONCLUSION: Multiple triple-route Wharton's jelly-derived MSC administrations were found to be safe for HIE patients, indicating neurological and functional improvement. Based on the findings obtained here, further randomized and placebo research could be performed.

Functional Recovery After Wharton's Jelly-Derived Mesenchymal Stem Cell Administration in a Patient with Traumatic Brain Injury: A Pilot Study.

AIM: To introduce a traumatic brain injury (TBI) patient who underwent stem cell transplantation (SCT) in order to minimize the remaining injury deficiencies. MATERIAL AND METHODS: This study included a 29 years old male who had TBI resulting from a vehicle accident which took place one and a half years ago. The participant received six doses of intrathecal, intramuscular, and intravenous transplantation of Wharton?s jellv-derived mesenchymal stem cells (WJ-MSCs) at a goal dose of 1xl0 < sup > 6 < /sup > / kg respectively for each route of administration for six months. RESULTS: No important negative effects were reported. The patients? speech, cognitive, memory and fine motor skills were improved. The efficacy of treatment with SCT was assessed with cranial magnetic resonance imaging (MRI), computed tomography (CT) screening, and electroencephalography (EEG). CONCLUSION: SCT can have a promising future as a medical approach in recurrent TBI.

Kyphoplasty in the Early Oncologic Diagnosis and Treatment of Vertebral Fractures: A Clinical Study.

AIM: To elucidate the characteristics of kyphoplasty in correlation with spinal metastasis. MATERIAL AND METHODS: Data of patients treated by kyphoplasty between January 2017 and December 2019 were reviewed retrospectively. Preoperative prophylactic antibiotics and low-molecular-weight heparin injections were performed. Postoperative follow-up was conducted at least 24 hours after the procedure. All patients were treated under sedoanalgesia. Bone biopsies were collected from all patients. RESULTS: One hundred ninety-nine vertebra fractures were treated in 130 patients. The mean age of the patients was 65.27 ± 8.79 years (18?90 years) and 66 patients were male (50.7%). Forty-five patients had osteoporosis, six patients showed malignancy, and osteomyelitis was found in three patients, while the others? presentations were secondary to trauma. Most commonly, the L1 (n=59), Th12 (n=45), and L2 (n=34) levels were found to develop vertebral fractures. Forty patients had multiple levels of vertebral fracture, with a higher rate of osteoporosis (n=24; 60%). Three patients showed undiagnosed oncologic disease with an initial diagnosis of acute fracture following minor trauma, while the primary oncologic diagnosis was established by bone biopsy taken during the routine procedure in each procedure (e.g., plasmacytoma, lymphoma, adenocarcinoma of the lung). None of the patients developed an infection due to kyphoplasty, permanent neuromotor deficit, or mortality. The mean postoperative hospital length of stay was 1.6 days. CONCLUSION: Bone biopsy should be performed to diagnose early spinal metastases. Although an accurate bone biopsy may not be obtained from some patients, particularly from those with osteoporosis, performing bone biopsy during the procedure does not cause time loss or any other complications, and protects the surgeon from possible medicolegal problems.

Challenges in the Clinical and Radiological Differential Diagnosis of Cerebrovascular Events and Malignant Primary Brain Tumors: Reports from a Retrospective Case Series.

AIM: To reveal difficulties in differential diagnosis of some cases of cerebrovascular events (CVEs) and malignant primary brain tumors (MBTs) even a multidiciplinary evaluation in grand rounds. MATERIAL AND METHODS: This study retrospectively analyzed the patient archives from January 2017?December 2019. The records of 572 patients discussed in these meetings were examined. A total of 8 patients having a challenge in differential diagnosis were detected. RESULTS: This study has included 8 cases in which neurology-neurosurgery-neuroradiology clinicians have difficulty in differentiating CVE and MBT. In the present study, three patients were evaluated with a preliminary diagnosis of hemorrhagic CVE in the emergency room. Since degradation products of hemoglobin have prevented advanced imaging methods to diagnose in two patients, these patients have been followed closely. The correct diagnosis could be made through the scan performed during control follow-ups The preliminary diagnosis of seven patients was CVE, but they received the MBT diagnosis during the follow-up. One patient was thought to have MBT initially; however, he/she was diagnosed with CVE after an advanced examination and close follow-up. CONCLUSION: Despite developing medical imaging methods and diagnostic studies, there are still some difficulties in making differential diagnosis of CVEs and MBTs. In some patients, further examination and imaging methods may be needed such as magnetic resonance imaging-spectroscopy (MRI-S), perfusion magnetic resonance imaging (Per-MRI), digital substratioangiography (DSA). Despite all these neuroradiological examinations and multidiciplinary evaluation, distinction between CVE and MBT may be difficult, and medicolegal problems may be encountered.

Physical impacts of PLGA scaffolding on hMSCs: Recovery neurobiology insight for implant design to treat spinal cord injury.

Our earlier work generated a powerful platform technology of polymeric scaffolding of stem cells to investigate and treat the injured or diseased central nervous system. However, the reciprocal sequelae between biophysical properties of the polymer and responses of the stem cell have not been examined in situ in lesioned spinal cords. We postulated that implantable synthetic scaffolds, acting through physical features, might affect donor cell behavior and host tissue remodeling. To test this hypothesis, poly(d,l-lactic-co-glycolic acid) (PLGA) in either low/soft or high/hard rigidity was fabricated for carrying adult human bone marrow mesenchymal stromal stem cells (hMSCs). The construct was transplanted into the epicenter of a rat model of acute T9-10 segmental hemisection to evaluate the effect of PLGA rigidity on the therapeutic potential and fate of hMSCs for neural repair. Compared to controls, only treatment with soft PLGA-scaffolded hMSCs significantly improved sensorimotor function via activation of recovery neurobiology mechanisms. The main benefits included inhibiting neuroinflammation and enhancing tissue protection. Also detected in the treated lesion region were expressions of neurotrophic and anti-inflammatory factors together with proliferation of endogenous neural stem cells, impacts likely derived from hMSCs' functional multipotency maintained by soft PLGA-scaffolding. Conversely, hard rigidity PLGA activated mechanotransduction and mesoderm lineage differentiation of hMSCs that ectopically produced bone, cartilage and muscle markers in neural parenchyma. The findings collectively suggested that the physical texture of polymeric scaffolds should be tailored for sustaining the stemness of hMSCs to constructively interact with the spinal cord for functional restoration.

Reduction of Inflammation and Enhancement of Motility after Pancreatic Islet Derived Stem Cell Transplantation Following Spinal Cord Injury.

OBJECTIVE: Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestinpositive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI. METHODS: rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, S100ß, brain derived neurotrophic factor (BDNF), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor [TGF]-ß, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors. RESULTS: rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), ß3-tubulin and nestin as well as antiinflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined. CONCLUSION: Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

Radiofrequency Thermocoagulation of the Ganglion Impar for Coccydynia Management: Long-Term Effects.

OBJECTIVE: To investigate the short- and long-term effects of ganglion impar radiofrequency thermocoagulation (RFT) treatment in patients with chronic coccydynia. METHODS: We retrospectively analyzed the medical records of patients who underwent RFT of the ganglion impar between 2009 and 2011. Pain intensity visual numeric scale (VNS) scores and Euroqol 5D (EQ-5D) index scores were recorded pre-intervention and post-intervention at the first, sixth, and twelfth months. The differences between pre-procedural VNS scores and post-procedural VNS scores at the first, sixth, and twelfth months were evaluated. The success of the intervention was recorded as the percentage difference between the pre-intervention VNS scores and post-intervention VNS scores at the first, sixth, and twelfth months. RESULTS: The mean age of the patients, including 11 females (55%) and 8 males (45%), was 48.7 ± 14.3 years. The average follow-up duration was 17.3 ± 2.9 months. Statistically significant differences were observed between the pre- and post-procedure VNS scores (P < 0.0001). Improvements in VNS scores were correlated with improvements in EQ-5D index scores. Mid-term (sixth month) and long-term (twelfth month) evaluations after the intervention revealed that 67.4% and 61.1% of the patients had successful outcomes, respectively. CONCLUSION: Our data suggested that RFT of the ganglion impar in patients with chronic coccydynia resulted in effective outcomes, and patients who responded to RFT had significantly lower post-RFT pain scores.

Wharton's Jelly-Derived Mesenchymal Stem Cell Transplantation in a Patient with Hypoxic-Ischemic Encephalopathy: A Pilot Study.

Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have been introduced as a possible therapy in hypoxic-ischemic encephalopathy (HIE). We report a 16-year-old boy who was treated with WJ-MSCs in the course of HIE due to post-cardiopulmonary resuscitation. He received a long period of mechanical ventilation and tracheostomy with spastic quadriparesis. He underwent the intrathecal (1×106/kg in 3 mL), intramuscular (1×106/kg in 20 mL) and intravenous (1×106/kg in 30 mL) administrations of WJ-MSCs for each application route (twice a month for 2 months). After stem cell infusions, progressive improvements were shown in his neurological examination, neuroradiological, and neurophysiological findings. To our best knowledge, this is a pioneer project to clinically study the neural repair effect of WJ-MSCs in a patient with HIE.

Updates on Human Neural Stem Cells: From Generation, Maintenance, and Differentiation to Applications in Spinal Cord Injury Research.

Human neural stem cells (hNSCs) and human induced pluripotent stem cells (hiPSCs) have been the primary focuses in basic science and translational research as well as in investigative clinical applications. Therefore, the capability to perform reliable derivation, effective expansion, and long-term maintenance of uncommitted hNSCs and hiPSCs and their targeted phenotypic differentiations through applying chemically and biologically defined medium in vitro is essential for expanding and enriching the fundamental and technological capacities of stem cell biology and regenerative medicine. In this chapter, we systematically summarized a set of protocols and unique procedures that have been developed in the laboratories of Prof. Teng and his collaborators. These regimens have been, over the years, reproducibly and productively used to derive, propagate, maintain, and differentiate hNSCs, including those derived from hiPSCs. We emphasize the multimodal methodologies that were pioneered and established in our laboratories for characterizing functional multipotency of stem cells and its value in basic science as well as translational biomedical studies.

Cancer Stem Cells or Tumor Survival Cells?

Research endeavors originally generated stem cell definitions for the purpose of describing normally sustainable developmental and tissue turnover processes in various species, including humans. The notion of investigating cells that possess a vague capacity of "stamm (phylum)" can be traced back to the late 19th century, mainly concentrating on cells that could produce the germline or the entire blood system. Lately, such undertakings have been recapitulated for oncogenesis, tumor growth, and cancer cell resistance to oncolytic therapies. However, due to the complexity and basic life-origin mechanisms comprising the genetic and epigenetic repertoire of the stemness in every developing or growing cell, presently there are ongoing debates regarding the biological essentials of the stem cell-like tumor initiation cells (ie, cancer stem cells; CSCs). This conceptual analysis focuses on the potential pitfalls of extrapolating that CSCs bear major traits of stemness. We propose a novel nomenclature of Tumor Survival Cells (TSCs) to further define tumor cells behaving like CSCs, based on the ruthless and detrimental features of Cancer Cell Survivology that appears fundamentally different from stem cell biology. Hence, precise academic separation of TSCs from all the stem cell-related labels applied to these unique tumor cells may help to improve scientific reasoning and strategies to decode the desperado-like survival behaviors of TSCs to eventually overcome cancer.

Establishing an Organotypic System for Investigating Multimodal Neural Repair Effects of Human Mesenchymal Stromal Stem Cells.

Human mesenchymal stromal stem cells (hMSCs) hold regenerative medicine potential due to their availability, in vitro expansion readiness, and autologous feasibility. For neural repair, hMSCs show translational value in research on stroke, spinal cord injury (SCI), and traumatic brain injury. It is pivotal to establish multimodal in vitro systems to investigate molecular mechanisms underlying neural actions of hMSCs. Here, we describe a platform protocol on how to set up organotypic co-cultures of hMSCs (alone or polymer-scaffolded) with explanted adult rat dorsal root ganglia (DRGs) to determine neural injury and recovery events for designing implants to counteract neurotrauma sequelae. We emphasize in vitro hMSC propagation, polymer scaffolding, hMSC stemness maintenance, hMSC-DRG interaction profiling, and analytical formulas of neuroinflammation, trophic factor expression, DRG neurite outgrowth and tropic tracking, and in vivo verification of tailored implants in rodent models of SCI. © 2018 by John Wiley & Sons, Inc.

The Effects of Adipose Tissue-Derived Mesenchymal Stem Cell Transplantation During the Acute and Subacute Phases Following Spinal Cord Injury.

AIM: To investigate the effectiveness of rat adipose tissue-derived (rAT) mesenchymal stem cell (MSC) transplantation on the functional restoration and regeneration of spinal cord injury (SCI). MATERIAL AND METHODS: Six of 48 Wistar albino rats were sacrificed to obtain MSCs, and the remaining rats were divided randomly into six groups. SCI was performed using the clip compression method. The control and transplantation groups were injected with physiological saline and a rAT-MSC suspension at the injury sites, respectively. Each animal was evaluated using the Basso, Beattie and Bresnahan (BBB) rating system and sacrificed at 28 days post-injury period (p.i.). The regeneration process was evaluated based on immunostaining against ß3-tubulin, BDNF, CNTF, and CNPase. RESULTS: rAT-MSC transplantation into the SCI site substantially improved the tissue regeneration and functional recovery (p < 0.05). However, the rAT-MSC transplantation at 9 days p.i. was not more efficient on functional recovery than the transplantation immediately after injury. The expression of ß3-tubulin, BDNF and CNTF at the injury site indicated the potential for functional regeneration. CONCLUSION: The adaptive nature of rat-MSCs enabled the remodulation and regeneration of the lesion site, decreasing the importance of transplantation time in the treatment of SCI.

Biological approaches to treating intervertebral disk degeneration: devising stem cell therapies.

Intervertebral disk (IVD) degeneration is a common, chronic, and complex degeneration process that frequently leads to back pain and disability, resulting in a major public health issue. In this review we describe biological therapies under preclinical or clinical development with an emphasis on stem cell-based multimodal approaches that target prevention and treatment of IVD degeneration. Systematical review of the basic science and clinical literature was performed to summarize the current status of devising biological approaches to treating IVD degeneration. Since the exact mechanisms underlying IVD degeneration have not yet been fully elucidated and conservative managements appear to be mostly ineffective, current surgical treatment focuses on removal of the pathological disk tissues combined with spinal fusion. The treatment options, however, often produce insufficient efficacy and even serious complications. Therefore, there have been growing demands and endeavors for developing novel regenerative biology-guided strategies for repairing the IVD via delivery of exogenous growth factors, introduction of therapeutic genes, and transplantation of stem cells, or combinatorial therapies. Overall, the data suggest that when applied under a recovery neurobiology principle, multimodal regimens comprising ex vivo engineered stem cell-based disks hold a high potential promise for efficacious clinical translations.