Comparative analysis of curative effect of CT-guided stem cell transplantation and open surgical transplantation for sequelae of spinal cord injury

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Abstract

Background

This study compared the clinical efficacies, advantages and disadvantages of two transplantation approaches for treating spinal cord injury: open surgical exploration combined with local stem cell transplantation (referred to as open surgical transplantation) and local stem cell transplantation by CT-guided puncture (referred to as CT-guided transplantation).

Methods

The patients were divided into the following three groups to perform a retrospective controlled study: Group A included nine patients who underwent open surgical transplantation, Group B included nine patients who underwent CT-guided transplantation, and Group C included nine patients who did not receive stem cell transplantation. The Abbreviated Injury Scale (AIS), the American Spinal Injury Association (ASIA) score and the motor evoked potentials (MEP) examination were utilized to compare the differences in the clinical efficacies. The advantages and disadvantages of the two transplantation approaches were also compared, including the surgical risks, the possibility of repeating the operation, the interval between surgery and rehabilitation exercises and the scope of conditions suitable for the operation.

Results

Whether evaluated by the AIS grading scale, the ASIA score or the MEP results, there were significant differences in the clinical efficacy among the three patient groups. Group B exhibited the best clinical outcome, followed by Group A, and Group C fared the worst. The CT-guided transplantation had the advantages of lower surgical risk, the potential to repeat the operations within a short time-frame and a short interval between surgery and rehabilitation exercise compared with the open surgical transplantation. The conditions that are suitable for CT-guided transplantation versus the conditions suitable for open surgical transplantation are not identical. The application scopes for the two approaches had their respective strengths.

Conclusions

CT-guided stem cell transplantation was confirmed as a safe and effective approach to treat sequelae of spinal cord injury with the advantages of simpler operation, minimal invasion, less adverse reaction and quicker recovery.

Trial registration

Clinical trials registration number: ChiCTR-TNRC-12002477.

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Most cited references 14

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Interleukin-10 Prevents Diet-Induced Insulin Resistance by Attenuating Macrophage and Cytokine Response in Skeletal Muscle

Eun-Gyoung Hong, Hwi-Jin Ko, You-Ree Cho … (2009)

OBJECTIVE Insulin resistance is a major characteristic of type 2 diabetes and is causally associated with obesity. Inflammation plays an important role in obesity-associated insulin resistance, but the underlying mechanism remains unclear. Interleukin (IL)-10 is an anti-inflammatory cytokine with lower circulating levels in obese subjects, and acute treatment with IL-10 prevents lipid-induced insulin resistance. We examined the role of IL-10 in glucose homeostasis using transgenic mice with muscle-specific overexpression of IL-10 (MCK-IL10). RESEARCH DESIGN AND METHODS MCK-IL10 and wild-type mice were fed a high-fat diet (HFD) for 3 weeks, and insulin sensitivity was determined using hyperinsulinemic-euglycemic clamps in conscious mice. Biochemical and molecular analyses were performed in muscle to assess glucose metabolism, insulin signaling, and inflammatory responses. RESULTS MCK-IL10 mice developed with no obvious anomaly and showed increased whole-body insulin sensitivity. After 3 weeks of HFD, MCK-IL10 mice developed comparable obesity to wild-type littermates but remained insulin sensitive in skeletal muscle. This was mostly due to significant increases in glucose metabolism, insulin receptor substrate-1, and Akt activity in muscle. HFD increased macrophage-specific CD68 and F4/80 levels in wild-type muscle that was associated with marked increases in tumor necrosis factor-α, IL-6, and C-C motif chemokine receptor-2 levels. In contrast, MCK-IL10 mice were protected from diet-induced inflammatory response in muscle. CONCLUSIONS These results demonstrate that IL-10 increases insulin sensitivity and protects skeletal muscle from obesity-associated macrophage infiltration, increases in inflammatory cytokines, and their deleterious effects on insulin signaling and glucose metabolism. Our findings provide novel insights into the role of anti-inflammatory cytokine in the treatment of type 2 diabetes.

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Stem cells and neurological diseases.

D Hess, C V Borlongan (2007)

Cells of the central nervous system were once thought to be incapable of regeneration. This dogma has been challenged in the last decade with studies showing new, migrating stem cells in the brain in many rodent injury models and findings of new neurones in the human hippocampus in adults. Moreover, there are reports of bone marrow-derived cells developing neuronal and vascular phenotypes and aiding in repair of injured brain. These findings have fuelled excitement and interest in regenerative medicine for neurological diseases, arguably the most difficult diseases to treat. There are numerous proposed regenerative approaches to neurological diseases. These include cell therapy approaches in which cells are delivered intracerebrally or are infused by an intravenous or intra-arterial route; stem cell mobilization approaches in which endogenous stem and progenitor cells are mobilized by cytokines such as granulocyte colony stimulatory factor (GCSF) or chemokines such as SDF-1; trophic and growth factor support, such as delivering brain-derived neurotrophic factor (BDNF) or glial-derived neurotrophic factor (GDNF) into the brain to support injured neurones; these approaches may be used together to maximize recovery. While initially, it was thought that cell therapy might work by a 'cell replacement' mechanism, a large body of evidence is emerging that cell therapy works by providing trophic or 'chaperone' support to the injured tissue and brain. Angiogenesis and neurogenesis are coupled in the brain. Increasing angiogenesis with adult stem cell approaches in rodent models of stroke leads to preservation of neurones and improved functional outcome. A number of stem and progenitor cell types has been proposed as therapy for neurological disease ranging from neural stem cells to bone marrow derived stem cells to embryonic stem cells. Any cell therapy approach to neurological disease will have to be scalable and easily commercialized if it will have the necessary impact on public health. Currently, bone marrow-derived cell populations such as the marrow stromal cell, multipotential progenitor cells, umbilical cord stem cells and neural stem cells meet these criteria the best. Of great clinical significance, initial evidence suggests these cell types may be delivered by an allogeneic approach, so strict tissue matching may not be necessary. The most immediate impact on patients will be achieved by making use of the trophic support capability of cell therapy and not by a cell replacement mechanism.

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Repetitive intrathecal catheter delivery of bone marrow mesenchymal stromal cells improves functional recovery in a rat model of contusive spinal cord injury.

I Novotná, Ján Rosocha, Lucia Slovinska … (2011)

Transplantation of bone marrow mesenchymal stromal cells (MSCs) has been shown to improve the functional recovery in various models of spinal cord injury (SCI). However, the issues of the optimal dose, timing, and route of MSC application are crucial factors in achieving beneficial therapeutic outcomes. The objective of this study was to standardize the intrathecal (IT) catheter delivery of rat MSCs after SCI in adult rats. MSCs labeled with PKH-67 were administered by IT delivery to rats at 3 or 7 days after SCI as one of the following treatment regimens: (1) a single injection (5×10(5) MSCs/rat), or (2) as three daily injections (5×10(5) MSCs/rat/d for a total of 1.5×10(6) MSCs/rat over 3 days, injected on days 3, 4, and 5, or days 7, 8, and 9 following SCI. The animals were behaviorally tested for 4 weeks using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, and histologically assessed for MSC survival, distribution, and engraftment properties after 28 days. Rats treated with a single injection of MSCs at 3 or 7 days post-injury showed a modest, non-significant improvement in function and low survival of grafted MSCs, which were found attached to the pia mater or accumulated around the anterior spinal artery. In contrast, rats treated with three daily injections of MSCs at days 7, 8, and 9, but not on days 3, 4, and 5, showed significantly higher motor function recovery (BBB score 16.8±1.7) at 14-28 days post-injury. Transplanted PKH-67 MSCs were able to migrate and incorporate into the central lesion. However, only a limited number of surviving MSCs, ranging from 24,128±1170 to 116,258±8568 cells per graft, were observed within the damaged white matter. These results suggest that repetitive IT transplantation, which imposes a minimal burden on the animals, may improve behavioral function when the dose, timing, and targeted IT delivery of MSCs towards the lesion cavity are optimized.

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Author and article information

Journal

Journal ID (nlm-ta): J Transl Med

Journal ID (iso-abbrev): J Transl Med

Title: Journal of Translational Medicine

Publisher: BioMed Central

ISSN (Electronic): 1479-5876

Publication date Collection: 2013

Publication date (Electronic): 20 December 2013

Volume: 11

Page: 315

Affiliations

[1 ]Department of Cell Transplantation, General Hospital of Chinese people’s Armed Police Forces, Yongding Road, No. 69, Hai Dian District, Beijing 100039, China

[2 ]Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Yongding Road, No. 69, Hai Dian District, Beijing 100730, PR China

[3 ]Department of CT Room Radiology, General Hospital of Chinese people’s Armed Police Forces, Yongding Road, No. 69, Hai Dian District, Beijing 100039, China

Article

Publisher ID: 1479-5876-11-315

DOI: 10.1186/1479-5876-11-315

PMC ID: 3878170

PubMed ID: 24355001

SO-VID: f3364f91-5564-41c5-a1ac-b146c2de725a

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Comparative analysis of curative effect of CT-guided stem cell transplantation and open surgical transplantation for sequelae of spinal cord injury

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Most cited references 14

Interleukin-10 Prevents Diet-Induced Insulin Resistance by Attenuating Macrophage and Cytokine Response in Skeletal Muscle

Stem cells and neurological diseases.

Repetitive intrathecal catheter delivery of bone marrow mesenchymal stromal cells improves functional recovery in a rat model of contusive spinal cord injury.

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