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

Vaquero, Jesús; Zurita, Mercedes; Rico, Miguel A.; Bonilla, Celia; Aguayo, Concepción; Montilla, Jesús; Bustamante, Salvador; Carballido, Joaquı́n; Marı́n, Esperanza; Martínez, Francisco Andrés García; Parajón, A.; Fernández, Cecilia A.; Reina, Laura de

doi:10.1016/j.jcyt.2016.05.003

Cited by 94 publications

(81 citation statements)

References 34 publications

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“…Intralesional transplantation of autologous MSCs in subjects with complete SCI is safe, is feasible, and may play some roles to promote neurological improvements [81, 82]. Consistently, an approach to personalized cell therapy in chronic SCI indicated that all patients experienced improvement, primarily in sensitivity and sphincter control, while intralesional motor activity, according to clinical and neurophysiological studies, obtained an improvement by more than 50% of the total 12 patients [83]. A case report indicated that MSC transplantation can partially promote recovery of deep sensory pathways as demonstrated by somatosensory evoked potential (SSEP) recording and alleviate neuropathic pain of a patient with traumatic complete cervical SCI [84].…”

Section: Function Of Msc Transplantation After Scimentioning

confidence: 99%

Roles of Mesenchymal Stem Cells in Spinal Cord Injury

Zhang

2017

Stem Cells International

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Spinal cord injury (SCI) represents one of the most complicated and heterogeneous pathological processes of central nervous system (CNS) impairments, which is still beyond functional regeneration. Transplantation of mesenchymal stem cells (MSCs) has been shown to promote the repair of the injured spinal cord tissues in animal models, and therefore, there is much interest in the clinical use of these cells. However, many questions which are essential to improve the therapy effects remain unanswered. For instance, the functional roles and related molecular regulatory mechanisms of MSCs in vivo are not yet completely determined. It is important for transplanted cells to migrate into the injured tissue, to survive and undergo neural differentiation, or to play neural protection roles by various mechanisms after SCI. In this review, we will focus on some of the recent knowledge about the biological behavior and function of MSCs in SCI. Meanwhile, we highlight the function of biomaterials to direct the behavior of MSCs based on our series of work on silk fibroin biomaterials and attempt to emphasize combinational strategies such as tissue engineering for functional improvement of SCI.

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Section: Function Of Msc Transplantation After Scimentioning

confidence: 99%

Roles of Mesenchymal Stem Cells in Spinal Cord Injury

Zhang

2017

Stem Cells International

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“…Tables 1-3 show the results of clinical trials using ASC transplantation (including one activated macrophage and two Schwann cell trials) in various phases of SCI according to the American Spinal Injury Association Impairment Scale (AIS). Although many SCI patients treated with ASCs showed no changes in terms of AIS, some studies reported improvements of two AIS grades (A→C or B→D) 1,14,23,26,27,34,40,45,47,51,59,64,67) . In addition, functional improvements such as walking 1,14,23,39,40,45,67) and bladder/bowel control 1,14,19,26,27,34,39,45,59,67) were used to reveal clinical change in several trials.…”

Section: Time Windows For Stem Cell Therapy In Scimentioning

confidence: 99%

“…In most of the clinical trials presented in Tables 1-3, researchers reported that their clinical trials were safe without mortalities or severe morbidities related to either procedures or transplanted cells. However, there were some reported complications which were not associated with the procedures or applied cells : fever 4,40,59,64) , urinary tract infection 2,19,27,59) , abnormal blood profiles 2,27,40,45) , transient hypertension 26) , vomiting 4,19) , pulmonary thromboembolism 27) , and general body ache 4) . On the contrary, some complications including transient neuropathic pain 2,26,27,29,37,67) , transient deterioration in sensorimotor symptoms 29,37,44,64) , cerebrospinal f luid leakage 67) , subarachnoid hemorrhage 67) and subcutaneous seroma 67) , might be related to stem cell delivering procedures.…”

Section: Safety Of Ascsmentioning

confidence: 99%

Current Status and Future Strategies to Treat Spinal Cord Injury with Adult Stem Cells

Jeong

Choi

Jeon

2020

J Korean Neurosurg Soc

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Spinal cord injury (SCI) is one of the most devastating conditions and many SCI patients suffer neurological sequelae. Stem cell therapies are expected to be beneficial for many patients with central nervous system injuries, including SCI. Adult stem cells (ASCs) are not associated with the risks which embryonic stem cells have such as malignant transformation, or ethical problems, and can be obtained relatively easily. Consequently, many researchers are currently studying the effects of ASCs in clinical trials. The environment of transplanted cells applied in the injured spinal cord differs between the phases of SCI; therefore, many researchers have investigated these phases to determine the optimal time window for stem cell therapy in animals. In addition, the results of clinical trials should be evaluated according to the phase in which stem cells are transplanted. In general, the subacute phase is considered to be optimal for stem cell transplantation. Among various candidates of transplantable ASCs, mesenchymal stem cells (MSCs) are most widely studied due to their clinical safety. MSCs are also less immunogenic than neural stem/progenitor cells and consequently immunosuppressants are rarely required. Attempts have been made to enhance the effects of stem cells using scaffolds, trophic factors, cytokines, and other drugs in animal and/or human clinical studies. Over the past decade, several clinical trials have suggested that transplantation of MSCs into the injured spinal cord elicits therapeutic effects on SCI and is safe; however, the clinical effects are limited at present. Therefore, new therapeutic agents, such as genetically enhanced stem cells which effectively secrete neurotrophic factors or cytokines, must be developed based on the safety of pure MSCs. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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“…Cell survival and enhancement in locomotor performance have been observed both after intravenous injection of one million cells in a volume of 0.5 mL of DMEM in a model of balloon compressive injury in rats and after transplantation of 600,000 cells in a volume of 6 μL directly into the injury site after contusive injury in rats [112]. Other studies have advocated intrathecal administration from 100 × 10 6 up to 230 × 10 6 cells followed by an additional 30 × 10 6 cell administration at 3 months [5], or the administration of two or three intrathecal injections with a median of 1.2 × 10 6 mesenchymal stem cells/kg body weight [6]. In a phase III clinical trial, limited efficacy has been proven after injecting 1.6 × 10 autologous mesenchymal stem cells into the intramedullary area at the injured level and 3.2 × 10 autologous mesenchymal stem cells into the subdural space.…”

Section: Quantity and Numbermentioning

confidence: 99%

“…Mesenchymal stem cells, in particular, are easy to isolate, can be rapidly expanded in culture and can be cryopreserved without loss of potency [3,4]. Clinical reports on their use have varied, starting from documenting their safety [5,6] up to limited clinical efficacy [7], even partial or complete efficacy [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Prerequisites for Mesenchymal Stem Cell Transplantation in Spinal Cord Injury

Amr¹

2017

Mesenchymal Stem Cells - Isolation, Characterization and Applications

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We have aimed at distinguishing obligatory prerequisites for mesenchymal stem cell transplantation in spinal cord injury from those prerequisites which are unnecessary or are prerequisites that have to be further investigated. Obligatory prerequisites include the following. First, the site of injury is extensively gliotic, constituting an unsuitable medium for stem cell transplantation. It has to be dissolved by neurolyzing agents, chondroitinase ABC as an example. Second, stem cells need a suitable biomaterial scaffold for their proper integration. Third, the biomaterial scaffold necessitates a tissue filler harboring stem cells, other cells and neurotrophic factors in a combinatorial approach. Fourth, the efficiency of mesenchymal stem cells themselves has to be increased (by reducing oxidative stress-induced apoptosis, by hypoxic preconditioning, by modulating the extracellular matrix and by other measures). Prerequisites that have to be further investigated include the ideal source, mode, quantity, time point and number of injections of mesenchymal stem cells; which growth factors and cells to be used in the combinatorial approach; transforming mesenchymal stem cells into motor neuron-like cells or Schwann cells; increasing the homing effect of stem cells and how to establish a continuous drug and cell delivery system.

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

Abstract: Personalized cell therapy with MSCs is safe and leads to clear improvements in clinical aspects and quality of life for patients with complete and chronically established paraplegia.

Cited by 94 publications

References 34 publications

Roles of Mesenchymal Stem Cells in Spinal Cord Injury

Roles of Mesenchymal Stem Cells in Spinal Cord Injury

Current Status and Future Strategies to Treat Spinal Cord Injury with Adult Stem Cells

Prerequisites for Mesenchymal Stem Cell Transplantation in Spinal Cord Injury

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