Intrathecal transplantation of autologous adipose-derived mesenchymal stem cells for treating spinal cord injury: A human trial

Hur, Junseok W.; Cho, Tai Hyoung; Park, Dong Hyuk; Lee, Jang Bo; Park, Jungyul; Chung, Yong Gu

doi:10.1179/2045772315y.0000000048

Cited by 125 publications

(101 citation statements)

References 39 publications

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“…Almost all organ system have been implicated in adipose‐derived cell therapy. The indication for treatment in the included studies was (in order count) soft tissue , gastrointestinal , musculoskeletal , rheumatological , ulcer/ischemic limb , urogenital , cardiac , neurological , immunological , pulmonary , and ophthalmological (Fig. A).…”

Section: Resultsmentioning

confidence: 99%

Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events

Toyserkani

Jørgensen

Tabatabaeifar

et al. 2017

Stem Cells Translational Medicine

110

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The popularity of adipose‐derived cell therapy has increased over the last decade, and the number of studies published annually is growing. However, concerns regarding safety in the setting of previous malignancy or the use of allogeneic cells have been raised. We therefore aimed to systematically review all clinical studies using adipose‐derived cell therapy to identify reported adverse events with a special focus on risk of thromboembolic, immunological, and oncological safety concerns. Our systematic search resulted in 70 included studies involving more than 1,400 patients that were treated with adipose‐derived cell therapy. Safety assessment method was not described in 32 of the included studies. For studies involving systemic or cardiac administration, one case of pulmonary thromboembolism and cases of both myocardial and cerebral infarctions were described. In the setting of allogeneic cell therapy studies, where the production of specific antibodies toward donor cells was examined, it was noted that 19%–34% of patients develop antibodies, but the consequence of this is unknown. With regard to oncological safety, only one case of breast cancer recurrence was identified out of 121 patients. Adipose‐derived cell therapy has so far shown a favorable safety profile, but safety assessment description has, in general, been of poor quality, and only adverse events that are looked for will be found. We encourage future studies to maintain a strong focus on the safety profile of cell therapy, so its safeness can be confirmed. stem cells translational medicine 2017;6:1786–1794

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Section: Resultsmentioning

confidence: 99%

Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events

Toyserkani

Jørgensen

Tabatabaeifar

et al. 2017

Stem Cells Translational Medicine

110

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“…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. It is challenging to directly compare the results of clinical trials between the subacute and chronic phases of SCI due to differences in the study design, population, and stem cell type.…”

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%

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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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“…In particular, adipose MSCs (AMSCs) are easily obtained and have excellent expansion capacities, as well as a unique immunomodulatory and paracrine competence able to modulate many of the detrimental effects elicited after acute SCI (Mazini, Rochette, Amine, & Malka, ; Menezes et al, ; Takahashi et al, ). These effects together with a proven preclinical efficacy and safety profile have paved the way for the clinical assessment of AMSCs in a variety of trials (Bajek et al, ; Hur et al, ; Jin et al, ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of human HC016 cell transplants on neuroprotection and functional recovery in a rat model of acute spinal cord injury

Maqueda

Rodríguez

2019

J Tissue Eng Regen Med

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Spinal cord injury (SCI) is a devastating event with huge personal and social costs, for which there is no effective treatment. Cell therapy constitutes a promising therapeutic approach for SCI; however, its clinical potential is seriously limited by their low survival in the hostile conditions encompassing the acute phase of SCI. Human HC016 (hHC016) cells, generated from expanded human adipose mesenchymal stem cells (hAMSCs) and pulsed with a patented protocol with hydrogen peroxide (H2O2), are expected to acquire improved resistance to oxidative environments which appears as a major limiting factor hampering the engrafting success. Our specific aim was to assess whether H2O2‐pulsed hHC016 cells had an improved survival and thus therapeutic efficacy in a rat contusion model of acute SCI when grafted 48 hr after injury. Functional recovery was evaluated up to 56 days post‐injury (dpi) by locomotor (open field test and CatWalk) and sensory (Von Frey and Hargreaves) tests. Besides, histological evaluation of transplanted cell survival and tissue protection/regeneration was also performed. Functional results showed a statistically significant improvement on locomotor recovery outcomes with hHC016 cells. Accordingly, superior cell survival in correlation with long‐term neuroprotection, higher axonal regeneration, and reduced astroglial and microglial reactivity was also observed with hHC016 cells. These results demonstrate an enhanced survival capacity of hHC016 cells resulting in improved functional and histological outcomes as compared with hAMSCs, indicating that hHC016 cell transplants may constitute a promising cell therapy for acute SCI.

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Intrathecal transplantation of autologous adipose-derived mesenchymal stem cells for treating spinal cord injury: A human trial

Abstract: Over the 8 months of follow-up, intrathecal transplantation of autologous ADMSCs for SCI was free of serious adverse events, and several patients showed mild improvements in neurological function. Patient selection, dosage, and delivery method of ADMSCs should be investigated further.

Cited by 125 publications

References 39 publications

Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events

Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events

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

Efficacy of human HC016 cell transplants on neuroprotection and functional recovery in a rat model of acute spinal cord injury

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