Cell-Based Therapies for Traumatic Brain Injury: Therapeutic Treatments and Clinical Trials.

Traumatic brain injury (TBI) represents physical damage to the brain tissue that induces transitory or permanent neurological disabilities. TBI contributes to 50% of all trauma deaths, with many enduring long-term consequences and significant medical and rehabilitation costs. There is currently no therapy to reverse the effects associated with TBI.

Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study.

Breast cancer (BC) is the most common tumour in women and one of the most important causes of cancer death worldwide. Radiation therapy (RT) is widely used for BC treatment. Some proteins have been identified as prognostic factors for BC (Ki67, p53, E-cadherin, HER2).

Bone Marrow-derived Mesenchymal Stem Cells and Chronic Allograft Disease in a Bronchiolitis Obliterans Animal Model.

Introduction: Bronchiolitis obliterans (BO) is the most common expression of chronic allograft dysfunction in lung transplantation. Moreover, BO represents the major cause of death in the long-term after this procedure. On the other hand, mesenchymal stem cells have been tested in animal models of BO aiming to interfere in its development.

Intrathecal cell therapy with autologous stromal cells increases cerebral glucose metabolism and can offer a new approach to the treatment of Alzheimer's type dementia.

Background Aims: After recent observations that intrathecal administration of autologous bone marrow mesenchymal stromal cells (MSCs) increases cerebral metabolism in patients with severe traumatic brain injury (TBI), we examined this type of cell therapy in Alzheimer's type dementia.

Methods: Three patients with clinical diagnosis of Alzheimer's disease received every 3 months 100million autologous MSCs by intrathecal route, until a total dose of 300million.

Results: During cell therapy the patients showed arrest in neurological deterioration and two of them manifested clear improvement of previous symptoms.

Intrathecal administration of autologous mesenchymal stromal cells for spinal cord injury: Safety and efficacy of the 100/3 guideline.

Background Aims: Cell therapy with autologous mesenchymal stromal cells (MSCs) in patients with spinal cord injury (SCI) is beginning, and the search for its better clinical application is an urgent need.

Methods: We present a phase 2 clinical trial in patients with chronic SCI who received three intrathecal administrations of 100 x 10 MSCs and were followed for 10 months from the first administration. Efficacy analysis was performed on nine patients, and safety analysis was performed on 11 patients.

Cell therapy with autologous mesenchymal stromal cells in post-traumatic syringomyelia.

Background Aims: Recently, clinical studies show that cell therapy with mesenchymal stromal cells (MSCs) improves the sequelae chronically established in paraplegic patients, being necessary to know which of them can obtain better benefit.

Methods: We present here a phase 2 clinical trial that includes six paraplegic patients with post-traumatic syringomyelia who received 300 million MSCs inside the syrinx and who were followed up for 6 months. Clinical scales, urodynamic, neurophysiological, magnetic resonance (MR) and studies of ano-rectal manometry were performed to assess possible improvements.

Cell Therapy as a New Approach to the Treatment of Posttraumatic Syringomyelia.

Background: Cell transplantation with autologous bone marrow-derived mesenchymal stromal cells (MSCs) seems to be a therapeutic promise for patients with established spinal cord injury, achieving improvement in their quality of life, but there is no experience with the application of this type of cell therapy in patients suffering posttraumatic syringomyelia.

Objective: To study the possible utility of cell therapy with autologous MSCs in posttraumatic syringomyelia.

Methods: A 40-year-old man with complete paraplegia since 1991 as a consequence of a Th4 vertebral fracture showed a great posttraumatic syringomyelia that extended up to C2 vertebral level, without signs of recent worsening.

Repeated subarachnoid administrations of autologous mesenchymal stromal cells supported in autologous plasma improve quality of life in patients suffering incomplete spinal cord injury.

Background Aims: Cell therapy with mesenchymal stromal cells (MSCs) offers new hope for patients suffering from spinal cord injury (SCI).

Methods: Ten patients with established incomplete SCI received four subarachnoid administrations of 30 × 10 autologous bone marrow MSCs, supported in autologous plasma, at months 1, 4, 7 and 10 of the study, and were followed until the month 12. Urodynamic, neurophysiological and neuroimaging studies were performed at months 6 and 12, and compared with basal studies.

Progressive increase in brain glucose metabolism after intrathecal administration of autologous mesenchymal stromal cells in patients with diffuse axonal injury.

Background Aims: Cell therapy in neurological disability after traumatic brain injury (TBI) is in its initial clinical stage. We describe our preliminary clinical experience with three patients with diffuse axonal injury (DAI) who were treated with intrathecal administration of autologous mesenchymal stromal cells (MSCs).

Methods: Three patients with established neurological sequelae due to DAI received intrathecally autologous MSCs.

Inexpensive Attachment Device for Cell Therapy Administration into Injured Spinal Cord.

Background: Cell therapy is configured as a promising strategy for the treatment of spinal cord injury (SCI), but it requires reliable systems to achieve microinjections with different rates and volumes, according to the different characteristics of the injured spinal cord tissue and the targets previously selected.

Objective: We sought to describe an original and inexpensive device for support of microinjection systems in the course of spinal cord surgery.

Methods: Our attachment device consists of an arch and a system of bars that can be fixed to the operating table and on which a microinjection pump can be displaced and fixed in the course of surgery.

An approach to personalized cell therapy in chronic complete paraplegia: The Puerta de Hierro phase I/II clinical trial.

Background Aims: Cell transplantation in patients suffering spinal cord injury (SCI) is in its initial stages, but currently there is confusion about the results because of the disparity in the techniques used, the route of administration, and the criteria for selecting patients.

Methods: We conducted a clinical trial involving 12 patients with complete and chronic paraplegia (average time of chronicity, 13.86 years; SD, 9.

Dual Strategy With Oral Phosphodiesterase Type 5 Inhibition and Intracavernosal Implantation of Mesenchymal Stem Cells Is Superior to Individual Approaches in the Recovery of Erectile and Cavernosal Functions After Cavernous Nerve Injury in Rats.

Introduction: Novel effective therapeutic strategies are necessary for treating erectile dysfunction secondary to cavernous nerve injury (CNI).

Aim: To functionally evaluate the benefits of long-term oral treatment with a phosphodiesterase type 5 inhibitor on the potential capacity of intracavernosal cell therapy to recover erectile function after CNI.

Methods: Bilateral crush CNI (BCNI) was produced in anesthetized male rats.

Hypofractionated Breast Radiation: Shorter Scheme, Lower Toxicity.

Background: We analyzed the toxicity and cosmetic outcomes for patients who had undergone 3-dimensional conformal radiotherapy with a hypofractionated schedule and identified the risk factors associated with such a schedule.

Materials And Methods: A total of 143 patients were treated for breast cancer (stage 0-III) with a hypofractionated radiation schedule after breast-conserving surgery from 2006 to 2011. Most patients received 42.

Is the subarachnoid administration of mesenchymal stromal cells a useful strategy to treat chronic brain damage?

Background Aims: Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Developing effective protocols for the administration of mesenchymal stromal cells (MSCs) is a promising therapeutic strategy to treat TBI. It is important to develop alternatives to direct parenchymal injection at the injury site because direct injection is an expensive and invasive technique.

Cell transplantation in paraplegic patients: the importance of properly assessing the spinal cord morphology.

Introduction: Cell transplantation in paraplegic patients is beginning, but scarce attention is paid to the morphology of lesions.

Material And Methods: We studied using magnetic resonance imaging (MRI) the morphology of the injured spinal cord in 200 patients with chronic and complete paraplegia after spinal cord injury (SCI) at the thoracic level.

Results: When it was possible to undertake a correct study of the lesion, approximately 35% of patients had images showing spinal cord transection or showed fine tracts of tissue that connected both edges of a virtually transected spinal cord.

Perilesional intrathecal administration of autologous bone marrow stromal cells achieves functional improvement in pigs with chronic paraplegia.

Background Aims: At present, on the basis of the great number of preclinical studies and preliminary clinical trials in humans, bone marrow stromal cell (BMSC) transplantation offers promise in the treatment of paraplegia. Nevertheless, there is not enough experience in humans about the best candidates for this type of cell therapy or details about the best parameters or best route of administration.

Methods: Two adult paraplegic pigs with chronic paraplegia were treated only with perilesional intrathecal administration of 40 × 10(6) autologous BMSC suspended in autologous plasma and followed for 1 year after cell transplantation.

Cell therapy with bone marrow stromal cells after intracerebral hemorrhage: impact of platelet-rich plasma scaffolds.

Background Aims: Cell therapy using bone marrow stromal cells (BMSCs) has been considered a promising strategy for neurologic sequelae after intracerebral hemorrhage (ICH). However, after intracerebral administration of BMSCs, most of the cells die, partly because of the absence of extracellular matrix. Intracerebral transplantation of BMSCs, supported in a platelet-rich plasma (PRP) scaffold, optimizes this type of cell therapy.

Complex form variant of dysembryoplastic neuroepithelial tumor of the cerebellum.

Dysembryoplastic neuroepithelial tumor (DNT) is a benign neoplasm with typical supratentorial location, but the possibility of these rare tumors can also be located in the posterior fossa must be taken into account. We report a 21-year-old woman that suffered gait instability, headache, and diplopia. On CT-scan, an intraparenchymatous cerebellar tumor was disclosed.

[Perspectives of cell therapy in sequelae from cerebrovascular accidents].

Introduction: Spontaneous intracerebral hemorrhage (ICH) is associated with mortality between 40 and 50% of cases. Among the survivors, only 10% are independent after one month, there is no effective treatment of sequelae, except for the limited possibilities providing for rehabilitation.

Objectives: We review the current experience with intracerebral transplantation of mesenchymal stem cells (MSCs) obtained from bone marrow as a potential treatment of neurological sequelae occurring after experimental ICH.

The severity of brain damage determines bone marrow stromal cell therapy efficacy in a traumatic brain injury model.

Background: Patients who survive traumatic brain injury (TBI) can undergo serious sensorial and motor function deficits. Once damage occurs, there is no effective treatment to bring patients to full recovery. Recent studies, however, show bone marrow stromal cells (BMSC) as a potential therapy for TBI.

The pig model of chronic paraplegia: a challenge for experimental studies in spinal cord injury.

The regenerative medicine techniques that are beginning to be applied to the nervous system have led to increased hope in the treatment of diseases that have been considered incurable and that require experimental models on which to test new therapeutic strategies. We present our experience with adult pigs (minipigs) that have undergone a traumatic spinal cord injury (SCI) experimental model, and that have been followed for 1 year. We describe the surgical aspects of our SCI model by acute compression and also describe protocols for daily care and rehabilitation that are necessary to maintain the paraplegic pigs in good health during the months following the injury.

Failure of delayed intravenous administration of bone marrow stromal cells after traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Currently, there is no effective strategy to treat the functional sequelae associated with TBI. Experimental evidence shows that the intravenous administration of bone marrow stromal cells (BMSC) during the first week after TBI prevents neurological deficits, but no experimental studies have shown evidence of the effect of intravenous BMSC on chronic brain injury sequelae.

Allogeneic bone marrow stromal cell transplantation after cerebral hemorrhage achieves cell transdifferentiation and modulates endogenous neurogenesis.

Background Aims: When a severe neurologic lesion occurs as a consequence of intracerebral hemorrhage (ICH), there is no effective treatment available for improving the outcome. However, cell therapy has opened new perspectives on reducing neurologic sequels subsequent to this disease.

Methods: In this study, ICH was induced by stereotactic injection of 0.

Late transplantation of allogeneic bone marrow stromal cells improves neurologic deficits subsequent to intracerebral hemorrhage.

Background Aims: Stem cell therapy seems to be a promising therapeutic tool for treating central nervous system (CNS) injuries. Bone marrow stromal cell (BMSC) transplantation influences functional outcome subsequent to intracerebral hemorrhage (ICH), and enhances endogenous neurogenesis in acute condition studies. We investigated whether late administration of BMSC improves functional deficits subsequent to ICH.

Functional recovery after severe CNS trauma: current perspectives for cell therapy with bone marrow stromal cells.

The aim of this paper is to identify current perspectives for cell therapy applied to traumatic injuries of the central nervous system (CNS). After using diverse types of cell therapy, at present there is a growing experimental evidence that transplantation of bone marrow stromal cells (BMSC) can be useful to reverse the sequels of trauma affecting the brain and spinal cord. Although we still do not know many details about how these cells achieve their beneficial effects, the application of BMSC in humans, for brain or spinal cord repair, is beginning.