Use of autologous mesenchymal stem cells derived from bone marrow for the treatment of naturally injured spinal cord in dogs

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-06-03T19:00:40Z No. of bitstreams: 1 Penha EM Use of autologous mesenchymal....pdf: 2482714 bytes, checksum: 9305f82a377d77d99f97b37e8abd25d3 (MD5)Made available in DSpace on 2014-06-03T19:00:40Z (GMT). No. of bitstreams: 1 Penha EM Use of autologous mesenchymal....pdf: 2482714 bytes, checksum: 9305f82a377d77d99f97b37e8abd25d3 (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Hospital de Medicina Veterinária. Escola de Medicina Veterinária e Zootecnia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil /Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade do Estado da Bahia. Departamento de Ciências da Vida. Salvador, BA, BrasilHospital Espanhol. Salvador, BA, BrasilA Arca Veterinária. Salvador, BA, BrasilEstácio-FIB. Centro Universitário Estácio da Bahia. Salvador, BA, BrasilEstácio-FIB. Centro Universitário Estácio da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Hospital de Medicina Veterinária. Escola de Medicina Veterinária e Zootecnia. Salvador, BA, BrasilCentro de Biotecnologia e Terapia Celular. Hospital São Rafael. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Centro de Biotecnologia e Terapia Celular. Hospital São Rafael. Salvador, BA, BrasilThe use of stem cells in injury repair has been extensively investigated. Here, we examined the therapeutic effects of autologous bone marrow mesenchymal stem cells (MSC) transplantation in four dogs with natural traumatic spinal cord injuries. MSC were cultured in vitro, and proliferation rate and cell viability were evaluated. Cell suspensions were prepared and surgically administered into the spinal cord. The animals were clinically evaluated and examined by nuclear magnetic resonance. Ten days after the surgical procedure and MSC transplantation, we observed a progressive recovery of the panniculus reflex and diminished superficial and deep pain response, although there were still low proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb movement responses. Each dog demonstrated an improvement in these gains over time. Conscious reflex recovery occurred simultaneously with moderate improvement in intestine and urinary bladder functions in two of the four dogs. By the 18th month of clinical monitoring, we observed a remarkable clinical amelioration accompanied by improved movement, in three of the four dogs. However, no clinical gain was associated with alterations in magnetic resonance imaging. Our results indicate that MSC are potential candidates for the stem cell therapy following spinal cord injury

Clinical neurofunctional rehabilitation of a cat with spinal cord injury after hemilaminectomy and autologous stem cell transplantation

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-10-10T18:48:18Z No. of bitstreams: 1 Penha E M Clinical neurofunctional....pdf: 2136226 bytes, checksum: dbc03a2ad5b0fe76db8bf8c5a57027cf (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2014-10-10T18:48:33Z (GMT) No. of bitstreams: 1 Penha E M Clinical neurofunctional....pdf: 2136226 bytes, checksum: dbc03a2ad5b0fe76db8bf8c5a57027cf (MD5)Made available in DSpace on 2014-10-10T19:17:40Z (GMT). No. of bitstreams: 1 Penha E M Clinical neurofunctional....pdf: 2136226 bytes, checksum: dbc03a2ad5b0fe76db8bf8c5a57027cf (MD5) Previous issue date: 2012Universidade Federal da Bahia. Escola de Medicina da Bahia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal da Bahia. Escola de Medicina da Bahia. Salvador, BA, Brasil.Universidade Federal da Bahia. Escola de Medicina da Bahia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal do Vale do São Francisco. Salvador, BA, Brasil.Universidade Federal da Bahia. Escola de Medicina da Bahia. Salvador, BA, Brasil.Faculdade Zacarias de Góes. Valença, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Stem cell-based therapy has been investigated in a number of degenerative and traumatic diseases, including spinal cord injury. In the present study, we investigated the use of autologous mesenchymal stem cells in the functional rehabilitation of a domestic cat presenting a compressive L1-L5 fracture. Bone marrow cells collected by puncture of the iliac crest were cultured to obtain mesenchymal stem cells three weeks before surgery. Hemilaminectomy was performed, followed by injection of the mesenchymal stem cells in the injured area. Clinical evaluation of the animal prior to surgery showed absence of pain, muscular tonus, and panniculi reflexes. Seven days after surgery and cell transplantation the examination revealed a progressive recovery of the panniculus reflexes and of the responses to superficial and deep pain stimuli despite the low proprioceptive and hyperreflexic ataxic hind limbs. Physiotherapy protocols were applied for clinical rehabilitation after surgery. The cat’s first steps, three-minute weight-bearing, and intestine and urinary bladder partial reestablishment were observed 75 days post-surgery. Our results indicate the therapeutic potential of mesenchymal stem cells in chronic spinal cord injuries

Safety and neurological assessments after autologous transplantation of bone marrow mesenchymal stem cells in subjects with chronic spinal cord injury.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-05-27T16:55:57Z No. of bitstreams: 1 Mendonça MVP Safety....pdf: 1520611 bytes, checksum: c73d72436dfa4e3a49b2829957c29b40 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-05-27T17:27:22Z (GMT) No. of bitstreams: 1 Mendonça MVP Safety....pdf: 1520611 bytes, checksum: c73d72436dfa4e3a49b2829957c29b40 (MD5)Made available in DSpace on 2015-05-27T17:27:22Z (GMT). No. of bitstreams: 1 Mendonça MVP Safety....pdf: 1520611 bytes, checksum: c73d72436dfa4e3a49b2829957c29b40 (MD5) Previous issue date: 2014Hospital Espanhol. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia, Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilCentro Universitário Estácio da Bahia. FIB. Salvador, BA, BrasilHospital Espanhol. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilINTRODUCTION: The administration of stem cells holds promise as a potential therapy for spinal cord injury (SCI). Mesenchymal stem cells have advantages for clinical applications, since they can be easily obtained, are suitable for autologous transplantation and have been previously shown to induce regeneration of the spinal cord in experimental settings. Here we evaluated the feasibility, safety and potential efficacy of autologous transplantation of mesenchymal stem cells in subjects with chronic complete SCI. METHOD: We conducted a phase I, non-controlled study in 14 subjects of both genders aging between 18 to 65 years, with chronic traumatic SCI (>6 months), at thoracic or lumbar levels, classified as American Spinal Injury Association (ASIA) A - complete injury. Baseline somatosensory evoked potentials (SSEP), spinal magnetic resonance imaging (MRI) and urodynamics were assessed before and after treatment. Pain rating was performed using the McGill Pain Questionnaire and a visual analogue score scale. Bone marrow-derived mesenchymal stem cells were cultured and characterized by flow cytometry, cell differentiation assays and G-band karyotyping. Mesenchymal stem cells were injected directly into the lesion following laminectomy and durotomy. RESULTS: Cell transplantation was an overall safe and well-tolerated procedure. All subjects displayed variable improvements in tactile sensitivity and eight subjects developed lower limbs motor functional gains, principally in the hip flexors. Seven subjects presented sacral sparing and improved American Spinal Injury Association impairment scale (AIS) grades to B or C - incomplete injury. Nine subjects had improvements in urologic function. One subject presented changes in SSEP 3 and 6 months after mesenchymal stem cells transplantation. Statistically significant correlations between the improvements in neurological function and both injury size and level were found. CONCLUSION: Intralesional transplantation of autologous mesenchymal stem cells in subjects with chronic, complete spinal cord injury is safe, feasible, and may promote neurological improvements. TRIAL REGISTRATION: ClinicalTrials.gov NCT01325103 - Registered 28 March 2011