An international team led by researchers at the University of California, San Diego School of Medicine reports that a single injection of human neural stem cells produced neuronal regeneration and improvement of function and mobility in rats impaired by an acute spinal cord injury (SCI).
The findings are published in the May 28, 2013 online issue of Stem Cell Research & Therapy.
Martin Marsala, MD, professor in the Department of Anesthesiology, with colleagues at UC San Diego and in Slovakia, the Czech Republic and The Netherlands, said grafting neural stem cells derived from a human fetal spinal cord to the rats' spinal injury site produced an array of therapeutic benefits -- from less muscle spasticity to new connections between the injected stem cells and surviving host neurons.
"The primary benefits were improvement in the positioning and control of paws during walking tests and suppression of muscle spasticity," said Marsala, a specialist in spinal cord trauma and spinal injury-related disorders. Spasticity -- exaggerated muscle tone or uncontrolled spasms -- is a serious and common complication of traumatic injury to the spinal cord.
The human stem cells, said the scientists, appeared to vigorously take root at the injury site.
"In all cell-grafted animals, there was robust engraftment, and neuronal maturation of grafted human neurons was noted," Marsala said. "Importantly, cysts or cavities that can form in or around spinal injuries were not present in any cell-treated animal. The injury-caused cavity was completely filled by grafted cells."
The rats received the pure stem cell grafts three days after injury (no other supporting materials were used) and were given drugs to suppress an immune response to the foreign stem cells. Marsala said grafting at any time after the injury appears likely to work in terms of blocking the formation of spinal injury cavities, but that more work would be required to determine how timing affects functional neurological benefit.
The grafted stem cells, according to Marsala, appear to be doing two things: stimulating host neuron regeneration and partially replacing the function of lost neurons.
"Grafted spinal stem cells are rich source of different growth factors which can have a neuroprotective effect and can promote sprouting of nerve fibers of the host neurons. We have also demonstrated that grafted neurons can develop contacts with the host neurons and, to some extent, restore the connectivity between centers, above and below the injury, which are involved in motor and sensory processing."
The scientists used a line of human embryonic stem cells recently approved for Phase 1 human trials in patients with chronic traumatic spinal injuries. Marsala said the ultimate goal is to develop neural precursor cells (capable of becoming any of the three main cell types in the nervous system) from induced pluripotent stem cells derived from patients, which would likely eliminate the need for immunosuppression treatment.
Pending approval by UC San Diego's Institutional Review Board, the next step is a small phase 1 trial to test safety and efficacy with patients who have suffered a thoracic spinal cord injury (between vertebrae T2-T12) one to two years earlier, and who have no motor or sensory function at or below the spinal injury site.
"This is exciting, especially because, historically, there has been very little to offer patients with acute spinal cord injury," said study co-author Joseph Ciacci, MD, professor of surgery and program director of the Neurosurgery Residency at the UC San Diego School of Medicine. Ciacci, who is also chief of neurosurgery for the Veterans Affairs San Diego Healthcare System, will oversee the clinical trial at UC San Diego and the VA.
Ciacci said if the initial study confirms safety and efficacy, as well as the viability of the implanted cells, neural regeneration and decreased spasticity, the protocol can be expanded to other patients with other forms of severe spinal cord injury.
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Timu ya kimataifa inayoongozwa na watafiti katika Chuo Kikuu cha California, San Diego School of Medicine, inaripoti kuwa sindano moja ya seli za msingi za neva za binadamu ilisababisha kuzaliwa upya kwa neva na kuboresha kazi na mwendo katika panya walioharibika na jeraha kali la uti wa mgongo. Utafiti huo ulichapishwa katika toleo la mtandaoni la Mei 28, 2013 la Stem Cell Research & Therapy. Martin Marsala, MD, profesa katika Idara ya Anesthesiology, na wenzake katika UC San Diego na Slovakia, Jamhuri ya Czech na Uholanzi, alisema kuunganisha seli za msingi za neva zinazotokana na utando wa mgongo wa binadamu kwa tovuti ya jeraha la mgongo wa panya ilitoa safu ya faida za matibabu - kutoka spasticity ndogo ya misuli hadi uhusiano mpya kati ya seli za msingi zilizopandikizwa na neuroni za mwenyeji. "Mafunzo ya msingi yalikuwa kuboresha nafasi na udhibiti wa paws wakati wa majaribio ya kutembea na kukandamiza spasticity ya misuli, ""alisema Marsala, mtaalamu wa majeraha ya uti wa mgongo na magonjwa yanayohusiana na majeraha ya uti wa mgongo." Spasticity - sauti ya misuli iliyoongezeka au mshtuko usioweza kudhibitiwa - ni tatizo zito na la kawaida la jeraha la uharibifu wa uti wa mgongo. Wanasayansi hao walisema kwamba chembe za msingi za binadamu zilionekana kuwa zimejiingiza kwa nguvu mahali pa jeraha hilo. "Katika wanyama wote waliopandikizwa chembe, kulikuwa na upandikizaji wenye nguvu, na kukomaa kwa neva za chembe za neva za binadamu zilizopandikizwa kulibainishwa", Marsala alisema. "Ni muhimu, cysts au cavities ambayo inaweza kuunda katika au karibu na majeraha ya uti wa mgongo hazikuwapo katika mnyama yeyote aliyetibiwa kwa seli. Mfupa uliosababishwa na jeraha ulijaa kabisa chembe zilizopandikizwa". Panya walipokea graft ya seli za msingi siku tatu baada ya kuumia (hakuna vifaa vingine vya kusaidia vilivyotumiwa) na walipewa dawa za kuzuia majibu ya kinga kwa seli za msingi za kigeni. Marsala alisema kuwa kuunganisha kwa wakati wowote baada ya jeraha linaonekana kuwa linafanya kazi katika suala la kuzuia malezi ya mashimo ya jeraha la uti wa mgongo, lakini kwamba kazi zaidi inahitajika kuamua jinsi wakati unavyoathiri faida ya neva ya kazi. Kwa mujibu wa Marsala, seli za shina zilizopandikizwa zinaonekana kufanya mambo mawili: kuchochea urekebishaji wa neva za mwenyeji na kubadilisha sehemu ya kazi ya neva zilizopotea. "Seli za shina za uti wa mgongo zilizopandikizwa ni chanzo tajiri cha sababu tofauti za ukuaji ambazo zinaweza kuwa na athari ya kinga ya neva na zinaweza kukuza kuota kwa nyuzi za neva za neuroni za mwenyeji. """ "Tumeonyesha pia kwamba nyuroni zilizopandikizwa zinaweza kuanzisha mawasiliano na nyuroni za mwenyeji na, kwa kiasi fulani, kurudisha uhusiano kati ya vituo, juu na chini ya jeraha, ambavyo vinahusika katika usindikaji wa motor na hisia. """ Wataalamu wa utafiti huo walitumia mstari wa seli za msingi za kiinitete za binadamu ambazo zimekubaliwa hivi karibuni kwa ajili ya majaribio ya awamu ya kwanza kwa wagonjwa wenye majeraha ya mhimili. Marsala alisema lengo la mwisho ni kuendeleza seli za neural precursor (kuweza kuwa yoyote ya aina tatu kuu za seli katika mfumo wa neva) kutoka kwa seli za asili za pluripotent zilizosababishwa kutoka kwa wagonjwa, ambayo inaweza kuondoa haja ya matibabu ya kinga. Baada ya idhini ya Bodi ya Mapitio ya Taasisi ya UC San Diego, hatua inayofuata ni jaribio dogo la awamu ya 1 kupima usalama na ufanisi na wagonjwa ambao wamepatwa na jeraha la uti wa mgongo wa kifua (kati ya vertebrae T2 na T2) mwaka mmoja hadi miaka miwili mapema na ambao hawana utendaji wa motor au hisia kwenye au chini ya jeraha la uti wa mgongo. "Hii ni ya kuvutia, hasa kwa sababu, kihistoria, imekuwa kidogo sana kutoa wagonjwa na majeraha ya uti wa mgongo, ""alisema utafiti mwandishi Joseph Ciacchi, MD, profesa wa upasuaji na mkurugenzi wa programu ya Neurosurgery Residency katika UC San Diego Shule ya Tiba." Ciacchi, ambaye pia ni mkuu wa upasuaji wa neva kwa Veterans Affairs San Diego Healthcare System, ataongoza jaribio la kliniki huko UC San Diego na VA, alisema ikiwa utafiti wa awali utathibitisha usalama na ufanisi, pamoja na uwezo wa seli zilizopandikizwa, kuzaliwa upya kwa neva na kupungua kwa spasticity, itifaki inaweza kupanuliwa kwa wagonjwa wengine wenye aina zingine za majeraha makali ya uti wa mgongo. Namba hii ya ukurasa: