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Canavero S, Lebenstein-Gumovski MV, Kim CY. The rise of transplantation neurosurgery: Spinal cord, eye, brain. Surg Neurol Int 2024; 15:478. [PMID: 39777173 PMCID: PMC11705158 DOI: 10.25259/sni_945_2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 11/14/2024] [Indexed: 01/11/2025] Open
Affiliation(s)
- Sergio Canavero
- HEAVEN/GEMINI International Collaborative Group, Turin, Italy
| | - Michail V. Lebenstein-Gumovski
- Neurosurgery Department, Sklifosovsky Clinical and Research Institute for Emergency Medicine, Moscow, Russian Federation
| | - C-Y Kim
- College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea
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2
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Nourbakhsh A, Takawira C, Barras E, Hampton C, Carossino M, Nguyen K, Gaschen L, Lopez MJ. A novel reconstruction model for thoracic spinal cord injury in swine. PLoS One 2024; 19:e0308637. [PMID: 39325721 PMCID: PMC11426471 DOI: 10.1371/journal.pone.0308637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Accepted: 07/25/2024] [Indexed: 09/28/2024] Open
Abstract
Spinal cord (SC) reconstruction (process to reestablish the severed neural continuity at the injury site) may provide better recovery from blunt SC injury (SCI). A miniature swine model of blunt SC compression was used to test the hypothesis that reconstruction of the SC with sural nerve in combination with surgical decompression and stabilization improves functional, macro- and microstructural recovery compared to decompression and stabilization alone. Following blunt T9-T11 SC compression injury, five adult Yucatan gilts randomly received laminectomy and polyethylene glycol (as fusogen) with (n = 3) or without (n = 2) sural nerve graft SC reconstruction. Fusogens are a heterogeneous collection of chemicals that fuse the axon membrane and are currently used to augment epineural coaptation during peripheral nerve graft reconstruction. Outcome measures of recovery included weekly sensory and motor assessments, various measurements obtained from computed tomography (CT) myelograms up to 12 weeks after injury Measurements from postmortem magnetic resonance imaging (MRI) and results from spinal cord histology performed 12 weeks after injury were also reported. Vertebral canal (VC), SC and dural sac (DS) dimensions and areas were quantified on 2-D CT images adjacent to the injury. Effort to stand and response to physical manipulation improved 7 and 9 weeks and 9 and 10 weeks, respectively, after injury in the reconstruction group. Myelogram measures indicated greater T13-T14 VC, smaller SC, and smaller DS dimensions in the reconstruction cohort, and increased DS area increased DS/VC area ratio, and higher contrast migration over time. Spinal cord continuity was evident in 2 gilts in the reconstruction cohort with CT and MRI imaging. At the SCI, microstructural alterations included axonal loss and glial scarring. Better functional outcomes were observed in subjects treated with sural nerve SC reconstruction. Study results support the use of this adult swine model of blunt SCI. Long-term studies with different nerve grafts or fusogens are required to expand upon these findings.
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Affiliation(s)
- Ali Nourbakhsh
- OrthoAtlanta, Stockbridge, Georgia, United States of America
| | - Catherine Takawira
- Department of Veterinary Clinical Science, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, United States of America
| | - Elise Barras
- University of Florida, Gainesville, Florida, United States of America
| | - Chiara Hampton
- Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, United States of America
| | - Mariano Carossino
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee, United States of America
| | - Khoivu Nguyen
- Department of Veterinary Clinical Science, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, United States of America
| | - Lorrie Gaschen
- Department of Veterinary Clinical Science, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, United States of America
| | - Mandi J Lopez
- Department of Veterinary Clinical Science, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, United States of America
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Scarabosio A, Surico PL, Tereshenko V, Singh RB, Salati C, Spadea L, Caputo G, Parodi PC, Gagliano C, Winograd JM, Zeppieri M. Whole-eye transplantation: Current challenges and future perspectives. World J Transplant 2024; 14:95009. [PMID: 38947970 PMCID: PMC11212585 DOI: 10.5500/wjt.v14.i2.95009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 04/24/2024] [Accepted: 05/15/2024] [Indexed: 06/13/2024] Open
Abstract
Whole-eye transplantation emerges as a frontier in ophthalmology, promising a transformative approach to irreversible blindness. Despite advancements, formidable challenges persist. Preservation of donor eye viability post-enucleation necessitates meticulous surgical techniques to optimize retinal integrity and ganglion cell survival. Overcoming the inhibitory milieu of the central nervous system for successful optic nerve regeneration remains elusive, prompting the exploration of neurotrophic support and immunomodulatory interventions. Immunological tolerance, paramount for graft acceptance, confronts the distinctive immunogenicity of ocular tissues, driving research into targeted immunosuppression strategies. Ethical and legal considerations underscore the necessity for stringent standards and ethical frameworks. Interdisciplinary collaboration and ongoing research endeavors are imperative to navigate these complexities. Biomaterials, stem cell therapies, and precision immunomodulation represent promising avenues in this pursuit. Ultimately, the aim of this review is to critically assess the current landscape of whole-eye transplantation, elucidating the challenges and advancements while delineating future directions for research and clinical practice. Through concerted efforts, whole-eye transplantation stands to revolutionize ophthalmic care, offering hope for restored vision and enhanced quality of life for those afflicted with blindness.
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Affiliation(s)
- Anna Scarabosio
- Department of Plastic Surgery, University Hospital of Udine, Udine 33100, Italy
- Department of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
| | - Pier Luigi Surico
- Schepens Eye Research Institute of Mass Eye and Ear, Harvard Medical School, Boston, MA 02114, United States
| | - Vlad Tereshenko
- Department of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
| | - Rohan Bir Singh
- Schepens Eye Research Institute of Mass Eye and Ear, Harvard Medical School, Boston, MA 02114, United States
| | - Carlo Salati
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
| | - Leopoldo Spadea
- Eye Clinic, Policlinico Umberto I, "Sapienza" University of Rome, Rome 00142, Italy
| | - Glenda Caputo
- Department of Plastic Surgery, University Hospital of Udine, Udine 33100, Italy
| | - Pier Camillo Parodi
- Department of Plastic Surgery, University Hospital of Udine, Udine 33100, Italy
| | - Caterina Gagliano
- Department of Medicine and Surgery, University of Enna "Kore", Enna 94100, Italy
- Eye Clinic Catania University San Marco Hospital, Viale Carlo Azeglio Ciampi 95121 Catania, Italy
| | - Jonathan M Winograd
- Department of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
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Shen T, Zhang W, Wang X, Ren X. Application of"Spinal cord fusion" in spinal cord injury repair and its neurological mechanism. Heliyon 2024; 10:e29422. [PMID: 38638967 PMCID: PMC11024622 DOI: 10.1016/j.heliyon.2024.e29422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 04/03/2024] [Accepted: 04/08/2024] [Indexed: 04/20/2024] Open
Abstract
Spinal cord injury (SCI) is a severely disabling and catastrophic condition that poses significant global clinical challenges. The difficulty of SCI repair results from the distinctive pathophysiological mechanisms, which are characterised by limited regenerative capacity and inadequate neuroplasticity of the spinal cord. Additionally, the formation of cystic cavities and astrocytic scars after SCI further obstructs both the ascending and descending neural conduction pathways. Consequently, the urgent challenge in post-SCI recovery lies in repairing the damaged spinal cord to reconstruct a functional and intact neural conduction circuit. In recent years, significant advancements in biological tissue engineering technology and novel therapies have resulted in a transformative shift in the field of SCI repair. Currently, SCI treatment primarily involves drug therapy, stem cell therapy, the use of biological materials, growth factors, and other approaches. This paper comprehensively reviews the progress in SCI research over the years, with a particular focus on the concept of "Spinal Cord Fusion" as a promising technique for SCI reconstruction. By discussing this important research progress and the neurological mechanisms involved, our aim is to help solve the problem of SCI repair as soon as possible and to bring new breakthroughs in the treatment of paraplegia after SCI.
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Affiliation(s)
- Tingting Shen
- Guangxi University of Chinese Medicine, Nanning, Guangxi, 530001, China
- Department of Orthopedics, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China
- Institute of Orthopedics, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China
- Global Initiative to Cure Paralysis (GICUP Alliance), Columbus, OH, 43221, United States
| | - Weihua Zhang
- Department of Orthopedics, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China
- Institute of Orthopedics, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China
- Global Initiative to Cure Paralysis (GICUP Alliance), Columbus, OH, 43221, United States
| | - Xiaogang Wang
- Guangxi University of Chinese Medicine, Nanning, Guangxi, 530001, China
- Department of Orthopedics, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China
- Institute of Orthopedics, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China
- Global Initiative to Cure Paralysis (GICUP Alliance), Columbus, OH, 43221, United States
| | - Xiaoping Ren
- Department of Orthopedics, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China
- Institute of Orthopedics, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China
- Global Initiative to Cure Paralysis (GICUP Alliance), Columbus, OH, 43221, United States
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Lebenstein-Gumovski M, Zharchenko A, Rasueva T, Bashahanov R, Kovalev DA, Zhirov A, Shatokhin A, Grin A. PEG-chitosan (Neuro-PEG) induced restoration of motor function after complete transection of the dorsal spinal cord in swine. A pilot study. Surg Neurol Int 2023; 14:424. [PMID: 38213450 PMCID: PMC10783697 DOI: 10.25259/sni_928_2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 12/01/2023] [Indexed: 01/13/2024] Open
Abstract
Background Spinal cord injury (SCI) remains an unmet medical need. Recently, fusogens, such as polyethylene glycol (PEG), have been proven effective in restoring sensorimotor function after complete transection of the spinal cord at different levels and in different species. Here, we report on the use of a PEG-chitosan combo in a different animal model (swine). Methods Five Hungarian Mangalica pigs were subjected to complete transection of the thoracic cord (T7-9). Three animals were treated with locally injected PEG-chitosan (Neuro-PEG) gel; two acted as controls. PEG-600 was also injected intra- and post-operatively intravenously. Animals were submitted to rehabilitation, including electrical myostimulation. Results were assessed after 60 days using the Individual Limb Motor Score, the Porcine Thoracic Spinal Cord Injured Behavioral Scale, and the modified motor Basso, Beattie, and Bresnahan scale; sensory and sphincter functions were also assessed. Animals underwent in vivo spinal cord tracing with DiI. Immunofluorescence histology included NF-200, DAPI, and a fluorochrome-conjugated secondary antibody. Results Starting on postoperative day (POD) 2, neuro-PEG-treated animals evinced the first signs of recovery, and on POD 60, they could all support their weight and were mobile. Controls never recovered any useful function. Fluorescence microscopy in the experimental group revealed axons passing through the site of injury, while degenerative post-traumatic changes were noted in controls. Conclusion Neuro-PEG affords sensorimotor recovery after complete spinal cord transection. This opens the door to human experimentation, including trials of spinal cord transplantation.
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Affiliation(s)
| | - Alexander Zharchenko
- Department of General Medicine, Stavropol State Medical University, Stavropol, Russian Federation
| | - Tanzila Rasueva
- Clinic of Neurosurgery, N.V. Sklifosovsky Research Institute for Emergency Medicine, Moscow Healthcare Department, Moscow, Russian Federation
| | - Robert Bashahanov
- Department of General Medicine, Stavropol State Medical University, Stavropol, Russian Federation
| | - Dmitry A. Kovalev
- Biochemistry Lab, Stavropol Research Institute for Plague Control, Stavropol, Russian Federation
| | - Andrey Zhirov
- Biochemistry Lab, Stavropol Research Institute for Plague Control, Stavropol, Russian Federation
| | - Anton Shatokhin
- Department of Neurology and Neurosurgery, Stavropol State Medical University, Stavropol, Russian Federation
| | - Andrey Grin
- Clinic of Neurosurgery, N.V. Sklifosovsky Research Institute for Emergency Medicine, Moscow Healthcare Department, Moscow, Russian Federation
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Lebenstein-Gumovski MV, Bashakhanov RM, Kovalev DA, Zhirov AM, Shatohkin AA, Botasheva VS, Grin AA. [Recovery of spinal cord functions after experimental complete crossection under the effect of chitosan polymeric compounds]. ZHURNAL VOPROSY NEIROKHIRURGII IMENI N. N. BURDENKO 2023; 87:36-44. [PMID: 37830467 DOI: 10.17116/neiro20238705136] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/14/2023]
Abstract
Currently, there is no effective method of treating complete spinal cord intersection. One of the promising experimental approaches is substances promoting repair and fusion of axonal membranes. OBJECTIVE To study clinical and functional recovery in experimental animals with transected spinal cord after management with photo-cross-linked chitosan in a homogeneous mixture with polyethylene glycol. MATERIAL AND METHODS We studied 20 rabbits with a model of complete spinal cord transection at the level of Th9. There were control and experimental groups (n=10; n=10). In the experimental group, we intraoperatively injected photo-cross-linked chitosan in a homogeneous mixture with polyethylene glycol. Neurological status was assessed using the modified Basso Beattie Bresnahan scale. Histological examination was performed after removing the animals from the experiment. RESULTS In the experimental group, significant regression of neurological disorders was accompanied by partial recovery of movements, sensitivity and control of pelvic functions by the 30th day of the experiment. There was no mortality in the experimental group. Paraplegia and anesthesia persisted in the control group while mortality was 40% (n=4). Histological analysis in the main group revealed axonal «bridges» in the area of injury and spread of DiI dye through this area. CONCLUSION These phenomena confirm the positive effect of chitosan and polyethylene glycol on functional recovery after experimental spinal cord injury. These data are consistent with histological findings.
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Affiliation(s)
| | | | - D A Kovalev
- Stavropol Research Institute for Plague Control, Stavropol, Russia
| | - A M Zhirov
- Stavropol Research Institute for Plague Control, Stavropol, Russia
| | - A A Shatohkin
- Stavropol State Medical University, Stavropol, Russia
| | - V S Botasheva
- Stavropol State Medical University, Stavropol, Russia
| | - A A Grin
- Sklifosovsky Research Institute for Emergency Care, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
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The Most Promising Biomarkers of Allogeneic Kidney Transplant Rejection. J Immunol Res 2022; 2022:6572338. [PMID: 35669103 PMCID: PMC9167141 DOI: 10.1155/2022/6572338] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 04/30/2022] [Indexed: 12/13/2022] Open
Abstract
Clinical transplantology is a constantly evolving field of medicine. Kidney transplantation has become standard clinical practice, and it has a significant impact on reducing mortality and improving the quality of life of patients. Allogenic transplantation induces an immune response, which may lead to the rejection of the transplanted organ. The gold standard for evaluating rejection of the transplanted kidney by the recipient's organism is a biopsy of this organ. However, due to the high invasiveness of this procedure, alternative diagnostic methods are being sought. Therefore, the biomarkers may play an essential predictive role in transplant rejection. A review of the most promising biomarkers for early diagnosis and prognosis prediction of allogenic kidney transplant rejection summarizes novel data on neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), C-X-C motif chemokine 10 (CXCL-10), cystatin C (CysC), osteopontin (OPN), and clusterin (CLU) and analyses the dynamics of changes of the biomarkers mentioned above in kidney diseases and the mechanism of rejection of the transplanted kidney.
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Iltis A. Heads, Bodies, Brains, and Selves: Personal Identity and the Ethics of Whole-Body Transplantation. THE JOURNAL OF MEDICINE AND PHILOSOPHY 2022; 47:257-278. [PMID: 35543469 DOI: 10.1093/jmp/jhab049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Plans to attempt what has been called a head transplant, a body transplant, and a head-to-body transplant in human beings raise numerous ethical, social, and legal questions, including the circumstances, if any, under which it would be ethically permissible to attempt whole-body transplantation (WBT) in human beings, the possible effect of WBT on family relationships, and how families should shape WBT decisions. Our assessment of many of these questions depends partially on how we respond to sometimes centuries-old philosophical thought experiments about personal identity. As with so much in bioethics, it is impossible to escape, or at least inadvisable to try to bypass, the relevant foundational philosophical concerns.
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Affiliation(s)
- Ana Iltis
- Department of Philosophy and Center for Bioethics, Health and Society, Wake Forest University, Winston-Salem, North Carolina, USA
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Li J, Li Y. The Ethics of Head Transplant from the Confucian Perspective of Human Virtues. THE JOURNAL OF MEDICINE AND PHILOSOPHY 2022; 47:230-239. [PMID: 35452097 DOI: 10.1093/jmp/jhab051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Head transplantation has ignited intense discussions about whether it should be done scientifically and ethically. This paper examines the ethics of head transplantation from a Confucian perspective and offers arguments against the permissibility of head transplantation. From a Confucian point of view, human beings are the most precious organisms in the world, and ren (benevolence) and li (propriety) are the basic moral principles of human beings. As long as head transplant technology remains underdeveloped, this procedure should not be done because it will pose a serious risk of harm to humans and thus violate the principles of Confucian ren and li. If head transplant technology matures to the point that it would be safe to try in humans, it still should not be performed because it would change the selfhood or identity of the head donor and the body donor and create a new person. Confucian personal virtues greatly depend on selfhood or personal identity, and selfhood or personal identity depend on one's body cultivation and mind rectification. Through the hard effort of body cultivation and mind rectification, one transforms one's selfhood or identity and personality. This selfhood, identity, and personality cannot be separated from one's body but are embedded in one's body. Thus, head transplant would destroy two persons' identities and result in a new person, and the characteristics of this new person's identity are still unknown.
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Affiliation(s)
- Jianhui Li
- School of Philosophy, Beijing Normal University, Beijing, China
| | - Yaming Li
- Institute of Philosophy, Chinese Academy of Social Science, Beijing, China
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10
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Ren S, Zhang W, Liu H, Wang X, Guan X, Zhang M, Zhang J, Wu Q, Xue Y, Wang D, Liu Y, Liu J, Ren X. Transplantation of a vascularized pedicle of hemisected spinal cord to establish spinal cord continuity after removal of a segment of the thoracic spinal cord: A proof-of-principle study in dogs. CNS Neurosci Ther 2021; 27:1182-1197. [PMID: 34184402 PMCID: PMC8446222 DOI: 10.1111/cns.13696] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 06/02/2021] [Accepted: 06/06/2021] [Indexed: 12/14/2022] Open
Abstract
Introduction Glial scar formation impedes nerve regeneration/reinnervation after spinal cord injury (SCI); therefore, removal of scar tissue is essential for SCI treatment. Aims To investigate whether removing a spinal cord and transplanting a vascularized pedicle of hemisected spinal cord from the spinal cord caudal to the transection can restore motor function, to aid in the treatment of future clinical spinal cord injuries. We developed a canine model. After removal of a 1‐cm segment of the thoracic (T10–T11) spinal cord in eight beagles, a vascularized pedicle of hemisected spinal cord from the first 1.5 cm of the spinal cord caudal to the transection (cut along the posterior median sulcus of the spinal cord) was transplanted to bridge the transected spinal cord in the presence of a fusogen (polyethylene glycol, PEG) in four of the eight dogs. We used various forms of imaging, electron microscopy, and histologic data to determine that after our transplantation of a vascular pedicled hemisection to bridge the transected spinal cord, electrical continuity across the spinal bridge was restored. Results Motor function was restored following our transplantation, as confirmed by the re‐establishment of anatomic continuity along with interfacial axonal sprouting. Conclusion Taken together, our findings suggest that SCI patients—who have previously been thought to have irreversible damage and/or paralysis—may be treated effectively with similar operative techniques to re‐establish electrical and functional continuity following SCI.
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Affiliation(s)
- Shuai Ren
- Hand and Microsurgery Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China.,Global Initiative to Cure Paralysis (GICUP), Columbus, OH, USA
| | - Weihua Zhang
- Global Initiative to Cure Paralysis (GICUP), Columbus, OH, USA.,Department of Orthopedics, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China.,Institute of Orthopedic, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
| | - HongMiao Liu
- Department of Pathology, The General Hospital of Heilongjiang Farms & Land Reclamation Administration Harbin, Harbin, China
| | - Xin Wang
- Department of Pathology, The General Hospital of Heilongjiang Farms & Land Reclamation Administration Harbin, Harbin, China
| | - Xiangchen Guan
- Hand and Microsurgery Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China
| | - Mingzhe Zhang
- Hand and Microsurgery Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China
| | - Jian Zhang
- Hand and Microsurgery Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China
| | - Qiong Wu
- Department of MR Diagnosis, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yan Xue
- Department of Orthopaedics, The Fifth Hospital of Harbin, Harbin, China
| | - Dan Wang
- Department of Pathology, The General Hospital of Heilongjiang Farms & Land Reclamation Administration Harbin, Harbin, China
| | - Yong Liu
- Department of Orthopaedics, The Fifth Hospital of Harbin, Harbin, China
| | - Jianyu Liu
- Hand and Microsurgery Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China
| | - Xiaoping Ren
- Global Initiative to Cure Paralysis (GICUP), Columbus, OH, USA.,Department of Orthopedics, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China.,Institute of Orthopedic, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
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11
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How Human Head Transplantation Could Alter the Legal Definition of Death. NEUROPHYSIOLOGY+ 2020. [DOI: 10.1007/s11062-020-09855-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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12
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Canavero S, Ren X. Advancing the technology for head transplants: From immunology to peripheral nerve fusion. Surg Neurol Int 2019; 10:240. [PMID: 31893141 PMCID: PMC6911682 DOI: 10.25259/sni_495_2019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 11/21/2019] [Indexed: 12/15/2022] Open
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13
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Fioranelli M, Sepehri A, Roccia MG, Linda C, Rossi C, Dawodo A, Vojvodic P, Lotti J, Barygina V, Vojvodic A, Wollina U, Tirant M, Thuong NV, Lotti T. Recovery of Brain in Chick Embryos by Growing Second Heart and Brain. Open Access Maced J Med Sci 2019; 7:3085-3089. [PMID: 31850128 PMCID: PMC6910787 DOI: 10.3889/oamjms.2019.777] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Revised: 07/06/2019] [Accepted: 07/07/2019] [Indexed: 11/14/2022] Open
Abstract
To recover chick embryos damaged the brain, two methods are presented. In both of them, somatic cells of an embryo introduced into an egg cell and an embryo have emerged. In one method, injured a part of the brain in the head of an embryo is replaced with a healthy part of the brain. In the second method, the heart of brain embryo dead is transplanted with the embryo heart. In this mechanism, new blood cells are emerged in the bone marrow and transmit information of transplantation to subventricular zone (SVZ) of the brain through the circulatory system. Then, SVZ produces new neural stem cells by a subsequent dividing into neurons. These neurons produce new neural circuits within the brain and recover the injured brain. To examine the model, two hearts of two embryos are connected, and their effects on neural circuits are observed.
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Affiliation(s)
- Massimo Fioranelli
- Department of Nuclear Physics, Sub-nuclear and Radiation, G. Marconi University, Rome, Italy
| | - Alireza Sepehri
- Department of Nuclear Physics, Sub-nuclear and Radiation, G. Marconi University, Rome, Italy
| | - Maria Grazia Roccia
- Department of Nuclear Physics, Sub-nuclear and Radiation, G. Marconi University, Rome, Italy
| | - Cota Linda
- Department of Nuclear Physics, Sub-nuclear and Radiation, G. Marconi University, Rome, Italy
| | - Chiara Rossi
- Department of Nuclear Physics, Sub-nuclear and Radiation, G. Marconi University, Rome, Italy
| | - Amos Dawodo
- Department of Nuclear Physics, Sub-nuclear and Radiation, G. Marconi University, Rome, Italy
| | - Petar Vojvodic
- Clinic for Psychiatric Disorders “Dr. Laza Lazarevic”, Belgrade, Serbia
| | - Jacopo Lotti
- Department of Nuclear Physics, Sub-nuclear and Radiation, G. Marconi University, Rome, Italy
| | - Victoria Barygina
- Department of Biomedical Experimental and Clinical Sciences, University of Florence, Florence, Italy
| | - Aleksandra Vojvodic
- Department of Dermatology and Venereology, Military Medical Academy, Belgrade, Serbia
| | - Uwe Wollina
- Department of Dermatology and Allergology, Städtisches Klinikum Dresden, Dresden, Germany
| | | | - Nguyen Van Thuong
- Vietnam National Hospital of Dermatology and Venereology, Hanoi, Vietnam
| | - Torello Lotti
- Department of Dermatology, University of G. Marconi, Rome, Italy
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Ren X, Kim CY, Canavero S. Bridging the gap: Spinal cord fusion as a treatment of chronic spinal cord injury. Surg Neurol Int 2019; 10:51. [PMID: 31528389 PMCID: PMC6743693 DOI: 10.25259/sni-19-2019] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 02/06/2019] [Indexed: 12/15/2022] Open
Abstract
Despite decades of animal experimentation, human translation with cell grafts, conduits, and other strategies has failed to cure patients with chronic spinal cord injury (SCI). Recent data show that motor deficits due to spinal cord transection in animal models can be reversed by local application of fusogens, such as Polyethylene glycol (PEG). Results proved superior at short term over all other treatments deployed in animal studies, opening the way to human trials. In particular, removal of the injured spinal cord segment followed by PEG fusion of the two ends along with vertebral osteotomy to shorten the spine holds the promise for a cure in many cases.
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Affiliation(s)
- Xiaoping Ren
- Hand and Microsurgery Center, Second Affiliated Hospital of Harbin Medical University, Nangang, Harbin, China
- State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Nangang, Harbin, China
- Heilongjiang Medical Science Institute, Harbin Medical University, Nangang, Harbin, China
| | - C-Yoon Kim
- Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea
| | - Sergio Canavero
- HEAVEN-GEMINI International Collaborative Group, Turin, Italy
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15
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Abstract
According to many, head transplantation is considered to be an extraordinary and impossible surgical procedure. However, nowadays, relevant literature and recent advances suggest that the first human head transplantation might be feasible. This innovative surgery promises a life-saving procedure to individuals who suffer from a terminal disease, but whose head and brain are healthy. Recently, the first cephalosomatic anastomosis in a human model was successfully performed, confirming the surgical feasibility of the procedure, but still not the real outcome. Skepticism and several considerations, including surgical, ethical and psychosocial issues, have emerged in the scientific community since this imaginary procedure seems to be more feasible than ever before.
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Affiliation(s)
- Grigorios Gkasdaris
- 4th Surgical Department, "G. Papanikolaou" General Hospital, Thessaloniki, Greece
| | - Theodossios Birbilis
- Department of Neurosurgery, University Hospital of Alexandroupolis, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
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16
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Suskin ZD, Giordano JJ. Body -to-head transplant; a "caputal" crime? Examining the corpus of ethical and legal issues. Philos Ethics Humanit Med 2018; 13:10. [PMID: 30005672 PMCID: PMC6045868 DOI: 10.1186/s13010-018-0063-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 07/05/2018] [Indexed: 06/08/2023] Open
Abstract
Neurosurgeon Sergio Canavero proposed the HEAVEN procedure - i.e. head anastomosis venture - several years ago, and has recently received approval from the relevant regulatory bodies to perform this body-head transplant (BHT) in China. The BHT procedure involves attaching the donor body (D) to the head of the recipient (R), and discarding the body of R and head of D. Canavero's proposed procedure will be incredibly difficult from a medical standpoint. Aside from medical doubt, the BHT has been met with great resistance from many, if not most bio- and neuroethicists.Given both the known challenges and unknown outcomes of HEAVEN, several important neuroethical and legal questions have emerged should Canavero be successful, including: (1) What are the implications for transplantology in the U.S., inclusive of issues of expense, distributive justice, organizational procedures, and the cost(s) of novel insight(s)? (2) How do bioethical and neuroethical principles, and legal regulations of human subject research apply? (3) What are the legal consequences for Canavero (or any other surgeon) performing a BHT? (4) What are the tentative implications for the metaphysical and legal identity of R should they survive post-BHT? These questions are analyzed, issues are identified, and several solutions are proposed in an attempt to re-configure HEAVEN into a safe, clinically effective, and thus (more) realistically viable procedure.Notably, the permissibility of conducting the BHT in China fosters additional, important questions, focal to (1) whether Western ethics and professional norms be used to guide the BHT - or any neuroscientific research and its use - in non-Western countries, such as China; (2) if the models of responsible conduct of research are identical, similar, or applicable to the intent and conduct of research in China; and (3) what economic and political implications (for China and other countries) are fostered if/when such avant garde techniques are successful.These questions are discussed as a further impetus to develop a globally applicable neuroethical framework that would enable both local articulation and cosmopolitan inquiry and oversight of those methods and approaches deemed problematic, if and when rendered in more international settings.
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Affiliation(s)
- Zaev D. Suskin
- Harvard Medical School Center for Bioethics, 641 Huntington Avenue, Boston, MA 02115 USA
- Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington, DC, 20057 USA
- Neuroethics Studies Program, Pellegrino Center for Clinical Bioethics, Bldg. D, Rm 238, 4000 Reservoir Road NW, Washington, DC, 20057 USA
| | - James J. Giordano
- Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington, DC, 20057 USA
- Neuroethics Studies Program, Pellegrino Center for Clinical Bioethics, Bldg. D, Rm 238, 4000 Reservoir Road NW, Washington, DC, 20057 USA
- Departments of Neurology and Biochemistry, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC, 20057 USA
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17
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Are We Ready for a Human Head Transplant? The Obstacles That Must Be Overcome. CURRENT TRANSPLANTATION REPORTS 2018. [DOI: 10.1007/s40472-018-0196-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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18
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Manjila S, Alambyan V, Singh G, Satish P, Geertman RT. From Hypothermia to Cephalosomatic Anastomoses: The Legacy of Robert White (1926-2010) at Case Western Reserve University of Cleveland. World Neurosurg 2018; 113:14-25. [PMID: 29408298 DOI: 10.1016/j.wneu.2018.01.175] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2017] [Revised: 01/22/2018] [Accepted: 01/23/2018] [Indexed: 10/17/2022]
Abstract
Dr. Robert J. White (1926-2010) was an eminent neurosurgeon and bioethicist, renowned for his classic work in hypothermia and pioneering mammalian head transplant experiments. He founded the Division of Neurosurgery at the Cleveland Metropolitan General Hospital (currently MetroHealth Medical Center, a level 1 trauma county hospital) and became the youngest full professor at the Case Western Reserve University in Cleveland, Ohio. With over 500 research articles to his credit, he founded the Brain Research Laboratory at what was then the Cleveland Metropolitan General Hospital, which was also home to future leaders in neurosurgery, neurosciences, and allied specialties. He transferred a healthy monkey head onto a surgically beheaded monkey body under deep hypothermic conditions drawing both laurels and criticisms alike. Despite a largely controversial neurosurgical research career, his original contributions to deep hypothermia have found profound clinical applications in modern trauma and vascular neurosurgery. The new fusogens and myelorrhaphy methods being tried in Europe hold promise for a future of reanastomosing 2 homologous or heterologous tracts in the neuraxis.
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Affiliation(s)
- Sunil Manjila
- Department of Neurosurgery, McLaren Bay Region Hospital, Michigan, USA.
| | - Vilakshan Alambyan
- Department of Neurosurgery, Metro Health Medical Center, Cleveland, Ohio, USA
| | - Gagandeep Singh
- Department of Neurosurgery, Metro Health Medical Center, Cleveland, Ohio, USA
| | - Priyanka Satish
- Department of Neurosurgery, Metro Health Medical Center, Cleveland, Ohio, USA
| | - Robert T Geertman
- Department of Neurosurgery, Metro Health Medical Center, Cleveland, Ohio, USA
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19
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Kim CY, Sikkema WKA, Kim J, Kim JA, Walter J, Dieter R, Chung HM, Mana A, Tour JM, Canavero S. Effect of Graphene Nanoribbons (TexasPEG) on locomotor function recovery in a rat model of lumbar spinal cord transection. Neural Regen Res 2018; 13:1440-1446. [PMID: 30106057 PMCID: PMC6108198 DOI: 10.4103/1673-5374.235301] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
A sharply transected spinal cord has been shown to be fused under the accelerating influence of membrane fusogens such as polyethylene glycol (PEG) (GEMINI protocol). Previous work provided evidence that this is in fact possible. Other fusogens might improve current results. In this study, we aimed to assess the effects of PEGylated graphene nanoribons (PEG-GNR, and called “TexasPEG” when prepared as 1wt% dispersion in PEG600) versus placebo (saline) on locomotor function recovery and cellular level in a rat model of spinal cord transection at lumbar segment 1 (L1) level. In vivo and in vitro experiments (n = 10 per experiment) were designed. In the in vivo experiment, all rats were submitted to full spinal cord transection at L1 level. Five weeks later, behavioral assessment was performed using the Basso Beattie Bresnahan (BBB) locomotor rating scale. Immunohistochemical staining with neuron marker neurofilament 200 (NF200) antibody and astrocytic scar marker glial fibrillary acidic protein (GFAP) was also performed in the injured spinal cord. In the in vitro experiment, the effects of TexasPEG application for 72 hours on the neurite outgrowth of SH-SY5Y cells were observed under the inverted microscope. Results of both in vivo and in vitro experiments suggest that TexasPEG reduces the formation of glial scars, promotes the regeneration of neurites, and thereby contributes to the recovery of locomotor function of a rat model of spinal cord transfection.
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Affiliation(s)
- C-Yoon Kim
- Department of Stem Cell Biology, School of Medicine, Konkuk University; Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea
| | - William K A Sikkema
- Department of Chemistry, Department of Materials Science and NanoEngineering, and The NanoCarbon Center, Rice University, Houston, TX, USA
| | - Jin Kim
- Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea
| | - Jeong Ah Kim
- Biomedical Omics Group, Korea Basic Science Institute, Cheongju-si, Chungbuk, Korea
| | - James Walter
- Research Service, Hines Veterans Administration Hospital, Hines, IL, USA
| | - Raymond Dieter
- Research Service, Hines Veterans Administration Hospital, Hines, IL, USA
| | - Hyung-Min Chung
- Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea
| | - Andrea Mana
- HEAVEN/GEMINI International Collaborative Group, Turin, Italy
| | - James M Tour
- Department of Chemistry, Department of Materials Science and NanoEngineering, and The NanoCarbon Center, Rice University, Houston, TX, USA
| | - Sergio Canavero
- HEAVEN/GEMINI International Collaborative Group, Turin, Italy
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20
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Restoration of motor function after operative reconstruction of the acutely transected spinal cord in the canine model. Surgery 2017; 163:976-983. [PMID: 29223327 DOI: 10.1016/j.surg.2017.10.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 09/20/2017] [Accepted: 10/11/2017] [Indexed: 11/22/2022]
Abstract
BACKGROUND Cephalosomatic anastomosis or what has been called a "head transplantation" requires full reconnection of the respective transected ends of the spinal cords. The GEMINI spinal cord fusion protocol has been developed for this reason. Here, we report the first randomized, controlled study of the GEMINI protocol in large animals. METHODS We conducted a randomized, controlled study of a complete transection of the spinal cord at the level of T10 in dogs at Harbin Medical University, Harbin, China. These dogs were followed for up to 8 weeks postoperatively by assessments of recovery of motor function, somato-sensory evoked potentials, and diffusion tensor imaging using magnetic resonance imaging. RESULTS A total of 12 dogs were subjected to operative exposure of the dorsal aspect of the spinal cord after laminectomy and longitudinal durotomy followed by a very sharp, controlled, full-thickness, complete transection of the spinal cord at T10. The fusogen, polyethylene glycol, was applied topically to the site of the spinal cord transection in 7 of 12 dogs; 0.9% NaCl saline was applied to the site of transection in the remaining 5 control dogs. Dogs were selected randomly to receive polyethylene glycol or saline. All polyethylene glycol-treated dogs reacquired a substantial amount of motor function versus none in controls over these first 2 months as assessed on the 20-point (0-19), canine, Basso-Beattie-Bresnahan rating scale (P<.006). Somatosensory evoked potentials confirmed restoration of electrical conduction cranially across the site of spinal cord transection which improved over time. Diffusion tensor imaging, a magnetic resonance permutation that assesses the integrity of nerve fibers and cells, showed restitution of the transected spinal cord with polyethylene glycol treatment (at-injury level difference: P<.02). CONCLUSION A sharply and fully transected spinal cord at the level of T10 can be reconstructed with restoration of many aspects of electrical continuity in large animals following the GEMINI spinal cord fusion protocol, with objective evidence of motor recovery and of electrical continuity across the site of transection, opening the way to the first cephalosomatic anastomosis. (Surgery 2017;160:XXX-XXX.).
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21
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Ren X, Li M, Zhao X, Liu Z, Ren S, Zhang Y, Zhang S, Canavero S. First cephalosomatic anastomosis in a human model. Surg Neurol Int 2017; 8:276. [PMID: 29279793 PMCID: PMC5705925 DOI: 10.4103/sni.sni_415_17] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 11/13/2017] [Indexed: 12/13/2022] Open
Abstract
Background: Cephalosomatic anastomosis (CSA) has never been attempted before in man as the transected spinal cords of the body donor and body recipient could not be “fused” back together. Recent advances made this possible. Here, we report on the surgical steps necessary to reconnect a head to a body at the cervical level. Methods: Full rehearsal of a CSA on two recently deceased human cadavers was performed at Harbin Medical University, Harbin, China. Results: The surgery took 18 hours to complete within the time frame planned for this surgery. Several advances resulted from this rehearsal, including optimization of the surgical steps, sparing of the main nerves (phrenics, recurrent laryngeal nerves), and assessment of vertebral stabilization. Conclusion: Several specialties are involved in a full-scale CSA, including neck surgery, vascular surgery, orthopedic surgery, plastic surgery, gastrointestinal surgery, and neurosurgery, as well as the operating staff. This rehearsal confirmed the surgical feasibility of a human CSA and further validated the surgical plan. Education and coordination of all the operating teams and coordination of the operative staff was achieved in preparation for the live human CSA.
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Affiliation(s)
- Xiaoping Ren
- Hand and Microsurgical Center, 2 Affiliated Hospital, Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China.,Heilongjiang Medical Science Institute, Harbin Medical University, Harbin, China.,Department of Molecular Pharmacology and Therapeutics, Stritch School of Medicine, Loyola University, Chicago, Illinois, USA
| | - Ming Li
- Hand and Microsurgical Center, 2 Affiliated Hospital, Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China.,Heilongjiang Medical Science Institute, Harbin Medical University, Harbin, China
| | - Xin Zhao
- Hand and Microsurgical Center, 2 Affiliated Hospital, Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China.,Heilongjiang Medical Science Institute, Harbin Medical University, Harbin, China
| | - Zehan Liu
- Hand and Microsurgical Center, 2 Affiliated Hospital, Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China.,Heilongjiang Medical Science Institute, Harbin Medical University, Harbin, China
| | - Shuai Ren
- Hand and Microsurgical Center, 2 Affiliated Hospital, Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China.,Heilongjiang Medical Science Institute, Harbin Medical University, Harbin, China
| | - Yafang Zhang
- Department of Anatomy, Harbin Medical University, Harbin, China
| | - Shide Zhang
- Department of Radiology, 2 Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Sergio Canavero
- Turin Advanced Neuromodulation Group, Turin, Italy, Harbin Medical University, Harbin, China
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22
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Miller LF. Transplanting the Body: Preliminary Ethical Considerations. New Bioeth 2017; 23:219-235. [PMID: 29058535 DOI: 10.1080/20502877.2017.1385919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
A dissociated area of medical research warrants bioethical consideration: a proposed transplantation of a donor's entire body, except head, to a patient with a fatal degenerative disease. The seeming improbability of such an operation can only underscore the need for thorough bioethical assessment: Not assessing a case of such potential ethical import, by showing neglect instead of facing the issue, can only compound the ethical predicament, perhaps eroding public trust in ethical medicine. This article discusses the historical background of full-body transplantation, documents the seriousness of its current pursuit, and builds an argument for why prima facie this type of transplant is bioethically distinct. Certainly, this examination can only be preliminary, indicating what should be a wide and vigorous discussion among practitioners and ethicists. It concludes with practical suggestions for how the medical and bioethics community may proceed with ethical assessment.
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23
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Iamsakul K, Pavlovcik AV, Calderon JI, Sanderson LM. PROJECT HEAVEN: Preoperative Training in Virtual Reality. Surg Neurol Int 2017; 8:59. [PMID: 28540125 PMCID: PMC5421260 DOI: 10.4103/sni.sni_371_16] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 01/10/2017] [Indexed: 01/05/2023] Open
Abstract
A cephalosomatic anastomosis (CSA; also called HEAVEN: head anastomosis venture) has been proposed as an option for patients with neurological impairments, such as spinal cord injury (SCI), and terminal medical illnesses, for which medicine is currently powerless. Protocols to prepare a patient for life after CSA do not currently exist. However, methods used in conventional neurorehabilitation can be used as a reference for developing preparatory training. Studies on virtual reality (VR) technologies have documented VR's ability to enhance rehabilitation and improve the quality of recovery in patients with neurological disabilities. VR-augmented rehabilitation resulted in increased motivation towards performing functional training and improved the biopsychosocial state of patients. In addition, VR experiences coupled with haptic feedback promote neuroplasticity, resulting in the recovery of motor functions in neurologically-impaired individuals. To prepare the recipient psychologically for life after CSA, the development of VR experiences paired with haptic feedback is proposed. This proposal aims to innovate techniques in conventional neurorehabilitation to implement preoperative psychological training for the recipient of HEAVEN. Recipient's familiarity to body movements will prevent unexpected psychological reactions from occurring after the HEAVEN procedure.
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Affiliation(s)
- Kiratipath Iamsakul
- Department of Biomedical Engineering, Inventum Bioengineering Technologies, LLC, Chicago, Illinois, USA
| | - Alexander V Pavlovcik
- Department of Biomedical Engineering, Inventum Bioengineering Technologies, LLC, Chicago, Illinois, USA
| | - Jesus I Calderon
- Department of Biomedical Engineering, Inventum Bioengineering Technologies, LLC, Chicago, Illinois, USA
| | - Lance M Sanderson
- Department of Biomedical Engineering, Inventum Bioengineering Technologies, LLC, Chicago, Illinois, USA
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24
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Furr A, Hardy MA, Barret JP, Barker JH. Surgical, ethical, and psychosocial considerations in human head transplantation. Int J Surg 2017; 41:190-195. [PMID: 28110028 PMCID: PMC5490488 DOI: 10.1016/j.ijsu.2017.01.077] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 01/11/2017] [Accepted: 01/14/2017] [Indexed: 12/14/2022]
Abstract
Transplanting a head and brain is perhaps the final frontier of organ transplantation. The goal of body-to-head transplantation (BHT) is to sustain the life of individuals who suffer from terminal disease, but whose head and brain are healthy. Ideally BHT could provide a lifesaving treatment for several conditions where none currently exists. BHT is no ordinary experiment, to transfer a head to another body involves extraordinarily complex medical challenges as well as ethical and existential dilemmas that were previously confined to the imagination of writers of fiction. The possibility of replacing an incurably ill body with a healthy one tests not only our surgical limits, but also the social and psychological boundaries of physical life and alters what we recognize life to be. The purpose of this target article, the complementary manuscript focused on immunological issues in BHT, and the accompanying Commentaries by scholars and practitioners in medicine, immunology, and bioethics is to review major surgical and psychosocial-ethical and immunological considerations surrounding body-to-head transplantation. We hope that together these ideas will provide readers with a comprehensive overview of the possibilities and challenges associated with BHT and initiate professional discussion and debate through which this new frontier in medicine is considered and approached.
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Affiliation(s)
- Allen Furr
- Haley Center 7018, Auburn University, Auburn, AL, 36849, USA.
| | - Mark A Hardy
- Department of Surgery, Columbia University College of Physicians and Surgeons, 161 Fort, Washington Ave., Herbert Irving Pavilion 5-549, New York, NY, 10032, USA.
| | - Juan P Barret
- University Hospital Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.
| | - John H Barker
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics & Trauma Surgery, J.W. Goethe-University, Friedrichsheim Orthopedic Hospital, Haus 97 B, 1OG, Marienburgstr. 2, 60528, Frankfurt/Main, Germany.
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25
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Li PW, Zhao X, Zhao YL, Wang BJ, Song Y, Shen ZL, Jiang HJ, Jin H, Canavero S, Ren XP. A cross-circulated bicephalic model of head transplantation. CNS Neurosci Ther 2017; 23:535-541. [PMID: 28429535 DOI: 10.1111/cns.12700] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Revised: 03/17/2017] [Accepted: 03/21/2017] [Indexed: 11/30/2022] Open
Abstract
AIMS A successful cephalosomatic anastomosis ("head transplant") requires, among others, the ability to control long-term immune rejection and avoidance of ischemic events during the head transference phase. We developed a bicephalic model of head transplantation to study these aspects. METHODS AND RESULTS The thoracic aorta and superior vena cava of a donor rat were anastomosed with the carotid artery and extracorporeal veins of a recipient rat by vascular grafts. Before thoracotomy in the donor rat, the axillary artery and vein of the donor were connected to the carotid and the extracranial vein of the third rat through a silicone tube. The silicone tube was passed through a peristaltic pump to ensure donor brain tissue blood supply. There is no ischemia reperfusion injury in donor brain tissue analyzed by electroencephalogram. Postoperative donor has pain reflex and corneal reflex. CONCLUSIONS Peristaltic pump application can guarantee the blood supply of donor brain tissue per unit time, while the application of temperature change device to the silicone tube can protect the brain tissue hypothermia, postoperative experimental data show that there is no brain tissue ischemia during the whole operation. The application of vascular grafting can also provide the possibility of long-term survival of the model.
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Affiliation(s)
- Peng-Wei Li
- Hand and Microsurgery Center, the Second Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, China
| | - Xin Zhao
- Hand and Microsurgery Center, the Second Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, China
| | - Yun-Long Zhao
- Hand and Microsurgery Center, the Second Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, China
| | - Bing-Jian Wang
- Hand and Microsurgery Center, the Second Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, China
| | - Yang Song
- Hand and Microsurgery Center, the Second Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, China
| | - Zi-Long Shen
- Hand and Microsurgery Center, the Second Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, China
| | - Hong-Jun Jiang
- Hand and Microsurgery Center, the Second Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, China
| | - Hai Jin
- Hand and Microsurgery Center, the Second Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, China
| | - Sergio Canavero
- HEAVEN/GEMINI International Collaborative Group, Turin, Italy
| | - Xiao-Ping Ren
- Hand and Microsurgery Center, the Second Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Nangang District, Harbin, China.,Department of Molecular Pharmacology and Therapeutics, Stritch School of Medicine, Loyola University, Maywood, IL, USA
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26
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Kim CY, Oh H, Ren X, Canavero S. Immunohistochemical evidence of axonal regrowth across polyethylene glycol-fused cervical cords in mice. Neural Regen Res 2017; 12:149-150. [PMID: 28250761 PMCID: PMC5319221 DOI: 10.4103/1673-5374.199014] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Affiliation(s)
- C-Yoon Kim
- Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea; Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea; Heaven/Gemini International Collaborative Group, Turin, Italy
| | - Hanseul Oh
- Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea; Heaven/Gemini International Collaborative Group, Turin, Italy
| | - Xiaoping Ren
- Hand and Microsurgical Center, the Second Affiliated Hospital of Harbin Medical University; State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, Heilongjiang Province, China; Heaven/Gemini International Collaborative Group, Turin, Italy
| | - Sergio Canavero
- Turin Advanced Neuromodulation Group, Turin, Italy; Heaven/Gemini International Collaborative Group, Turin, Italy
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27
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Abstract
Background Since the turn of the last century, the prospect of head transplantation has captured the imagination of scientists and the general public. Recently, head transplant has regained attention in popular media, as neurosurgeons have proposed performing this procedure in 2017. Given the potential impact of such a procedure, we were interested in learning the history of the technical hurdles that need to be overcome, and determine if it is even technically possible to perform such a procedure on humans today. Method We conducted a historical review of available literature on the technical challenges and developments of head transplantation. The many social, psychological, ethical, religious, cultural, and legal questions of head transplantation were beyond the scope of this review. Results Our historical review identified the following important technical considerations related to performing a head transplant: maintenance of blood flow to an isolated brain via vessel anastomosis; availability of immunosuppressive agents; spinal anastomosis and fusion following cord transfection; pain control in the recipient. Several animal studies have demonstrated success in maintaining recipient cerebral perfusion and achieving immunosuppression. However, there is currently sparse evidence in favor of successful spinal anastomosis and fusion after transection. While recent publications by an Italian group offer novel approaches to this challenge, research on this topic has been sparse and hinges on procedures performed in animal models in the 1970s. How transferrable these older methods are to the human nervous system is unclear and warrants further exploration. Conclusions Our review identified several important considerations related to performing a viable head transplantation. Besides the technical challenges that remain, there are important ethical issues to consider, such as exploitation of vulnerable patients and informed consent. Thus, besides the remaining technical challenges, these ethical issues will also need to be addressed before moving these studies to the clinic.
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28
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Canavero S, Ren X, Kim CY. HEAVEN: The Frankenstein effect. Surg Neurol Int 2016; 7:S623-5. [PMID: 27656323 PMCID: PMC5025952 DOI: 10.4103/2152-7806.190472] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Accepted: 07/29/2016] [Indexed: 11/23/2022] Open
Abstract
The HEAVEN head transplant initiative needs human data concerning the acute restoration of motor transmission after application of fusogens to the severed cord in man. Data from two centuries ago prove that a fresh cadaver, after hanging or decapitation, can be mobilized by electrical stimulation for up to 3 hours. By administering spinal cord stimulation by applied paddles to the cord or transcranial magnetic stimulation to M1 and recording motor evoked potentials, it should be possible to test fusogens in fresh cadavers. Delayed neuronal death might be the neuropathological reason.
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Affiliation(s)
- Sergio Canavero
- HEAVEN/GEMINI International Collaborative Group, Turin, Italy
| | - XiaoPing Ren
- HEAVEN/GEMINI International Collaborative Group, Turin, Italy
| | - C Yoon Kim
- HEAVEN/GEMINI International Collaborative Group, Turin, Italy
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Canavero S, Ren X. Houston, GEMINI has landed: Spinal cord fusion achieved. Surg Neurol Int 2016; 7:S626-8. [PMID: 27656324 PMCID: PMC5025958 DOI: 10.4103/2152-7806.190473] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 09/01/2016] [Indexed: 11/23/2022] Open
Affiliation(s)
- Sergio Canavero
- HEAVEN/GEMINI International Collaborative Group, Turin, Italy
| | - Xiaoping Ren
- HEAVEN/GEMINI International Collaborative Group, Turin, Italy
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Kim CY, Oh H, Hwang IK, Hong KS. GEMINI: Initial behavioral results after full severance of the cervical spinal cord in mice. Surg Neurol Int 2016; 7:S629-31. [PMID: 27656325 PMCID: PMC5025949 DOI: 10.4103/2152-7806.190474] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Accepted: 08/31/2016] [Indexed: 11/16/2022] Open
Abstract
Background: The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, we report the preliminary data on the use of a fusogen [polyethylene glycol (PEG)] after full cervical cord transection in mice to facilitate the fusion of both ends of a sharply transected spinal cord. Methods: Cervical laminectomy and a complete, visually confirmed cervical cord (C 5) transection was performed on female albino mice (n = 16). In Group 1 (n = 8), a fusogen, (PEG) was used to bridge the gap between the cut ends of the spinal cord. Group 2 received the same spinal cord transection but was treated with saline. Outcome was assessed daily using a standard scale (modified 22-point Basso-Beattie-Bresnahan scale) and filmed on camera. Results: The PEG group (group 1) showed partial restoration of motor function after 4 weeks of observation; group 2 (placebo) did not recover any useful motor activity. Conclusion: In this preliminary experiment, PEG, but not saline, promoted partial motor recovery in mice submitted to full cervical transection.
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Affiliation(s)
- C-Yoon Kim
- Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea; Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea
| | - Hanseul Oh
- Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea
| | - In-Kyu Hwang
- Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea
| | - Ki-Sung Hong
- Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea
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31
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Kim CY, Sikkema WKA, Hwang IK, Oh H, Kim UJ, Lee BH, Tour JM. Spinal cord fusion with PEG-GNRs (TexasPEG): Neurophysiological recovery in 24 hours in rats. Surg Neurol Int 2016; 7:S632-6. [PMID: 27656326 PMCID: PMC5025948 DOI: 10.4103/2152-7806.190475] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Accepted: 08/31/2016] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, for the first time, we report the effects of locally applied water-soluble, conductive PEG(polyethylene glycol)ylated graphene nanoribbons (PEG-GNRs) on neurophysiologic conduction after sharp cervical cord transection in rats. PEG-GNRs were produced by the polymerization of ethylene oxide from anion-edged graphene nanoribbons. These combine the fusogenic potential of PEG with the electrical conducting properties of the graphene nanoribbons. METHODS Laminectomy and transection of cervical spinal cord (C5) was performed on Female Sprague-Dawley (SD) rats. After applying PEG-GNR on the severed part, electrophysiological recovery of the reconstructed cervical spinal cord was confirmed by somatosensory evoked potentials (SSEPs) at 24 h after surgery. RESULTS While no SSEPs were detected in the control group, PEG-GNR treated group showed fast recovery of SSEPs at 24 h after the surgery. CONCLUSION In this preliminary dataset, for the first time, we report the effect of a novel form of PEG with the goal of rapid reconstruction of a sharply severed spinal cord.
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Affiliation(s)
- C-Yoon Kim
- Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea
- Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea
| | | | - In-Kyu Hwang
- Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea
| | - Hanseul Oh
- Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea
| | - Un Jeng Kim
- Department of Physiology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Bae Hwan Lee
- Department of Physiology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - James M. Tour
- Department of Chemistry, Rice University, Houston, Texas, USA
- The NanoCarbon Center, Rice University, Houston, Texas, USA
- Department of Material Science and Nanoengineering, Rice University, Houston, Texas, USA
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32
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Kim CY, Hwang IK, Kim H, Jang SW, Kim HS, Lee WY. Accelerated recovery of sensorimotor function in a dog submitted to quasi-total transection of the cervical spinal cord and treated with PEG. Surg Neurol Int 2016; 7:S637-40. [PMID: 27656327 PMCID: PMC5026027 DOI: 10.4103/2152-7806.190476] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Accepted: 08/31/2016] [Indexed: 11/12/2022] Open
Abstract
Background: A case report on observing the recovery of sensory-motor function after cervical spinal cord transection. Case Description: Laminectomy and transection of cervical spinal cord (C5) was performed on a male beagle weighing 3.5 kg. After applying polyethylene glycol (PEG) on the severed part, reconstruction of cervical spinal cord was confirmed by the restoration of sensorimotor function. Tetraplegia was observed immediately after operation, however, the dog showed stable respiration and survival without any complication. The dog showed fast recovery after 1 week, and recovered approximately 90% of normal sensorimotor function 3 weeks after the operation, although urinary disorder was still present. All recovery stages were recorded by video camera twice a week for behavioral analysis. Conclusion: While current belief holds that functional recovery is impossible after a section greater than 50% at C5-6 in the canine model, this case study shows the possibility of cervical spinal cord reconstruction after near-total transection. Furthermore, this case study also confirms that PEG can truly expedite the recovery of sensorimotor function after cervical spinal cord sections in dogs.
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Affiliation(s)
- C-Yoon Kim
- Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea
| | - In-Kyu Hwang
- Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea
| | - Hana Kim
- Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea
| | | | | | - Won-Young Lee
- Department of Food Bioscience, College of Biomedical and Health Science, Konkuk University, Chung-ju, Korea
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Ren X, Orlova EV, Maevsky EI, Bonicalzi V, Canavero S. Brain protection during cephalosomatic anastomosis. Surgery 2016; 160:5-10. [DOI: 10.1016/j.surg.2016.01.026] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2015] [Revised: 12/23/2015] [Accepted: 01/12/2016] [Indexed: 01/09/2023]
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Kim CY. PEG-assisted reconstruction of the cervical spinal cord in rats: effects on motor conduction at 1 h. Spinal Cord 2016; 54:910-912. [PMID: 27215738 PMCID: PMC5399165 DOI: 10.1038/sc.2016.72] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Affiliation(s)
- C-Y Kim
- Department of Bioengineering, College of Life Science, CHA University, Seoul, Korea.,Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea
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35
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Canavero S, Ren X, Kim CY, Rosati E. Neurologic foundations of spinal cord fusion (GEMINI). Surgery 2016; 160:11-19. [PMID: 27180142 DOI: 10.1016/j.surg.2016.01.027] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Revised: 01/08/2016] [Accepted: 01/21/2016] [Indexed: 12/17/2022]
Abstract
Cephalosomatic anastomosis has been carried out in both monkeys and mice with preservation of brain function. Nonetheless the spinal cord was not reconstructed, leaving the animals unable to move voluntarily. Here we review the details of the GEMINI spinal cord fusion protocol, which aims at restoring electrophysiologic conduction across an acutely transected spinal cord. The existence of the cortico-truncoreticulo-propriospinal pathway, a little-known anatomic entity, is described, and its importance concerning spinal cord fusion emphasized. The use of fusogens and electrical stimulation as adjuvants for nerve fusion is addressed. The possibility of achieving cephalosomatic anastomosis in humans has become reality in principle.
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Affiliation(s)
| | - XiaoPing Ren
- Hand and Microsurgical Center, the Second Affiliated Hospital of Harbin Medical University; State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China; Department of Molecular Pharmacology and Therapeutics, Stritch School of Medicine, Loyola University Chicago, Chicago, IL
| | - C-Yoon Kim
- Department of Bioengineering, College of Life Science, CHA University, Seoul, Korea; Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea
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Ye Y, Kim CY, Miao Q, Ren X. Fusogen-assisted rapid reconstitution of anatomophysiologic continuity of the transected spinal cord. Surgery 2016; 160:20-25. [PMID: 27138179 DOI: 10.1016/j.surg.2016.03.023] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Revised: 02/04/2016] [Accepted: 03/25/2016] [Indexed: 11/26/2022]
Abstract
The GEMINI spinal cord fusion protocol exploits the ability of so-called fusogens, such as polyethylene glycol (PEG), to achieve rapid neural restoration of electrical continuity across the ends of a transected spinal cord. Experimental evidence suggests that motor recovery can occur after complete transection of the cervical and dorsal spinal cord in mice and rats following application of PEG. This allows for the possibility of spinal cord "reconstruction" in humans and even the possibility of head transplantation in the future.
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Affiliation(s)
- Yijie Ye
- Hand and Microsurgical Center, 2nd Affiliated Hospital, Harbin Medical University, Harbin, China; State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China
| | - C-Yoon Kim
- College of Life Science, Department of Bioengineering, CHA University, Seoul, Korea; Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea
| | - Qing Miao
- Hand and Microsurgical Center, 2nd Affiliated Hospital, Harbin Medical University, Harbin, China; State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China
| | - Xiaoping Ren
- Hand and Microsurgical Center, 2nd Affiliated Hospital, Harbin Medical University, Harbin, China; State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China.
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37
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Affiliation(s)
- Xiao-Ping Ren
- Hand and Microsurgical Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China.,Department of Molecular Pharmacology & Therapeutics, Stritch School of Medicine, Loyola University Chicago, Chicago, IL, USA
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Canavero S, Ren XP. The Spark of Life: Engaging the Cortico-Truncoreticulo-Propriospinal Pathway by Electrical Stimulation. CNS Neurosci Ther 2016; 22:260-1. [PMID: 26888177 DOI: 10.1111/cns.12520] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Affiliation(s)
- Sergio Canavero
- Turin Advanced Neuromodulation Group (TANG), Turin, Italy.,Harbin Medical University, Harbin, China
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39
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Canavero S, Bonicalzi V. Central Pain Following Cord Severance for Cephalosomatic Anastomosis. CNS Neurosci Ther 2016; 22:271-4. [PMID: 26880305 DOI: 10.1111/cns.12527] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Revised: 01/24/2016] [Accepted: 01/25/2016] [Indexed: 11/30/2022] Open
Abstract
One of the key obstacles to a successful head transplant is the possible onset of central pain, a chronic pain condition that would impair the quality of life of the transplantee. In this review, we provide the reader with a knowledge of this neglected aspect of the head transplant initiative and outline the management should this eventuality occur.
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40
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Ren X, Canavero S. Human head transplantation. Where do we stand and a call to arms. Surg Neurol Int 2016; 7:11. [PMID: 26862450 PMCID: PMC4743270 DOI: 10.4103/2152-7806.175074] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2015] [Accepted: 11/27/2015] [Indexed: 11/04/2022] Open
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41
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Pascalev A, Pascalev M, Giordano J. Head Transplants, Personal Identity and Neuroethics. NEUROETHICS-NETH 2015. [DOI: 10.1007/s12152-015-9245-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Abstract
The term neuroethics defines the bioethics field that deals with the dilemmas arising from the development of the neurosciences. Why are we so sensitive to ponder on neuroethics? Because it involves the brain, the organ responsible for our perceptions, our thoughts, and our conscience; and its knowledge and/or manipulation entail the most genuine and nontransferable aspects of the human being. Since 2002, neuroethics has been recognized as a new discipline that offers an area of consideration for neuroscientific knowledge and the actions regarding human beings as individuals, and the society as an organization. Within its framework, we can distinguish two branches: fundamental neuroethics and applied neuroethics. Neuroethics demands that we are on alert, and we offer the possibility of interdisciplinary exchange programs, encouraging society to participate, promoting the ethical opinions, and even working with anticipation on the dilemmas that are already emerging. Science does not stop, and its development has acquired such an accelerated pace that there has not been enough time to discuss its processes. We are convinced that neuroethics will be for the 21(st) century, what genetics was for the 20(th) century.
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Affiliation(s)
- Alejandra T. Rabadán
- Division of Neurosurgery, Institute of Medical Research Dr. Alfredo Lanari, University of Buenos Aires and Academic Council on Ethics in Medicine, Argentina
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43
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Shanta BN. Life and consciousness - The Vedāntic view. Commun Integr Biol 2015; 8:e1085138. [PMID: 27066168 PMCID: PMC4802748 DOI: 10.1080/19420889.2015.1085138] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Revised: 08/16/2015] [Accepted: 08/17/2015] [Indexed: 11/04/2022] Open
Abstract
In the past, philosophers, scientists, and even the general opinion, had no problem in accepting the existence of consciousness in the same way as the existence of the physical world. After the advent of Newtonian mechanics, science embraced a complete materialistic conception about reality. Scientists started proposing hypotheses like abiogenesis (origin of first life from accumulation of atoms and molecules) and the Big Bang theory (the explosion theory for explaining the origin of universe). How the universe came to be what it is now is a key philosophical question. The hypothesis that it came from Nothing (as proposed by Stephen Hawking, among others), proves to be dissembling, since the quantum vacuum can hardly be considered a void. In modern science, it is generally assumed that matter existed before the universe came to be. Modern science hypothesizes that the manifestation of life on Earth is nothing but a mere increment in the complexity of matter — and hence is an outcome of evolution of matter (chemical evolution) following the Big Bang. After the manifestation of life, modern science believed that chemical evolution transformed itself into biological evolution, which then had caused the entire biodiversity on our planet. The ontological view of the organism as a complex machine presumes life as just a chance occurrence, without any inner purpose. This approach in science leaves no room for the subjective aspect of consciousness in its attempt to know the world as the relationships among forces, atoms, and molecules. On the other hand, the Vedāntic view states that the origin of everything material and nonmaterial is sentient and absolute (unconditioned). Thus, sentient life is primitive and reproductive of itself – omne vivum ex vivo – life comes from life. This is the scientifically verified law of experience. Life is essentially cognitive and conscious. And, consciousness, which is fundamental, manifests itself in the gradational forms of all sentient and insentient nature. In contrast to the idea of objective evolution of bodies, as envisioned by Darwin and followers, Vedānta advocates the idea of subjective evolution of consciousness as the developing principle of the world. In this paper, an attempt has been made to highlight a few relevant developments supporting a sentient view of life in scientific research, which has caused a paradigm shift in our understanding of life and its origin.
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Affiliation(s)
- Bhakti Niskama Shanta
- Sri Chaitanya Saraswat Institute; Govinda Shetty Palya, Konappana Agrahara; Electronic City , Bengaluru, Karnataka, India
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44
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Ren XP, Ye YJ, Li PW, Shen ZL, Han KC, Song Y. Head Transplantation in Mouse Model. CNS Neurosci Ther 2015; 21:615-8. [PMID: 26096690 DOI: 10.1111/cns.12422] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Revised: 05/17/2015] [Accepted: 05/22/2015] [Indexed: 01/24/2023] Open
Abstract
AIMS The mouse model of allo-head and body reconstruction (AHBR) has recently been established to further the clinical development of this strategy for patients who are suffering from mortal bodily trauma or disease, yet whose mind remains healthy. Animal model studies are indispensable for developing such novel surgical practices. The goal of this work was to establish head transplant mouse model, then the next step through the feasible biological model to investigate immune rejection and brain function in next step, thereby promoting the goal of translation of AHBR to the clinic in the future. METHODS AND RESULTS Our approach involves retaining adequate blood perfusion in the transplanted head throughout the surgical procedure by establishing donor-to-recipient cross-circulation by cannulating and anastomosing the carotid artery on one side of the body and the jugular vein on the other side. Neurological function was preserved by this strategy as indicated by electroencephalogram and intact cranial nerve reflexes. CONCLUSIONS The results of this study support the feasibility of this method for avoiding brain ischemia during transplantation, thereby allowing for the possibility of long-term studies of head transplantation.
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Affiliation(s)
- Xiao-Ping Ren
- Hand and Microsurgical Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China.,Department of Molecular Pharmacology & Therapeutics, Stritch School of Medicine, Loyola University Chicago, Chicago, IL, USA
| | - Yi-Jie Ye
- Hand and Microsurgical Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China
| | - Peng-Wei Li
- Hand and Microsurgical Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China
| | - Zi-Long Shen
- Hand and Microsurgical Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China
| | - Ke-Cheng Han
- Hand and Microsurgical Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China
| | - Yang Song
- Hand and Microsurgical Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.,State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China
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45
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Čartolovni A, Spagnolo AG. Ethical considerations regarding head transplantation. Surg Neurol Int 2015; 6:103. [PMID: 26110084 PMCID: PMC4476134 DOI: 10.4103/2152-7806.158785] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Accepted: 05/05/2015] [Indexed: 12/26/2022] Open
Affiliation(s)
- Anto Čartolovni
- Università Cattolica del S. Cuore (Catholic University of the Sacred Heart), "A. Gemelli" School of Medicine, Institute of Bioethics, 1, Largo Francesco Vito, I-00168 Rome, Italy
| | - Antonio G Spagnolo
- Università Cattolica del S. Cuore (Catholic University of the Sacred Heart), "A. Gemelli" School of Medicine, Institute of Bioethics, 1, Largo Francesco Vito, I-00168 Rome, Italy
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Canavero S. The "Gemini" spinal cord fusion protocol: Reloaded. Surg Neurol Int 2015; 6:18. [PMID: 25709855 PMCID: PMC4322377 DOI: 10.4103/2152-7806.150674] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Accepted: 11/17/2014] [Indexed: 01/13/2023] Open
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47
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Ren XP, Song Y, Ye YJ, Li PW, Han KC, Shen ZL, Shan JG, Luther K, Yang BF. Allogeneic head and body reconstruction: mouse model. CNS Neurosci Ther 2014; 20:1056-60. [PMID: 25367718 DOI: 10.1111/cns.12341] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Revised: 09/26/2014] [Accepted: 09/27/2014] [Indexed: 12/16/2022] Open
Abstract
AIMS There is still no effective way to save a surviving healthy mind when there is critical organ failure in the body. The next frontier in CTA is allo-head and body reconstruction (AHBR), and just as animal models were key in the development of CTA, they will be crucial in establishing the procedures of AHBR for clinical translation. METHODS AND RESULTS Our approach, pioneered in mice, involves retaining the donor brain stem and transplanting the recipient head. Our preliminary data in mice support that this allows for retention of breathing and circulatory function. Critical aspects of the current protocol include avoiding cerebral ischemia through cross-circulation (donor to recipient) and retaining the donor brain stem. Successful clinical translation of AHBR will become a milestone of medical history and potentially could save millions of people. CONCLUSIONS This experimental study has confirmed a method to avoid cerebral ischemia during the surgery and solved an important part of the problem of how to accomplish long-term survival after transplantation and preservation of the donor brain stem.
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Affiliation(s)
- Xiao-Ping Ren
- Hand and Microsurgical Center, the Second Affiliated Hospital of Harbin Medical University, Harbin, China; State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China; Department of Molecular Pharmacology & Therapeutics, Stritch School of Medicine, Loyola University Chicago, Chicago, IL, USA
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