ACTA VETERINARIA BRNO 审稿速度-刊鹿论文编译

Effect of human adipose-derived regenerative cells on temporomandibular joint healing in immunodeficient rabbits

Abstract:

Increasing research attention has focused on the use of stem cells (SCs) in regenerative and reparative medicine. Adipose-derived regenerative cells (ADRCs) are a relatively cheap and ethical source of SCs. Temporomandibular disorders (TMDs) have been reported with rising incidence over recent decades. The main aims of this study were to evaluate the effects of ADRCs application on the healing of both soft and hard temporomandibular joint (TMJ) tissues, and to assess the possible utilization of ADRCs in TMD treatment. We investigated the effects of human ADRCs on the healing of TMJ defects in immunodeficient rabbits. With no prior cultivation, ADRCs were applied to a surgically created defect in the cartilage of a rabbit TMJ. The healing process and inflammatory response were examined. Our results indicated that ADRCs supported repair processes in soft tissues. However, ADRC treatment induced a significant immune response in both soft and hard tissues, with hard tissues showing a higher level of bone remodelling. Non-differentiated ADRCs can be a promising tool for regenerative medicine of TMJ; however, deeper understanding of their effect on the cellular level is needed. Joint regeneration, allotransplantation, animal model The temporomandibular joint (TMJ) is a paired joint that connects the lower jaw to the temporal bone in mammals. A joint capsule attaches cranially to the temporal bone and caudally to the mandibular condyle neck, enclosing the entire articular system, including the condyle, articular disc, and fossa. This capsule is responsible for proprioception, articular structure nourishment, and prevention of joint dislocation (Berkovitz et al. 2009) The articular disc is located inside the TMJ, and divides it into two compartments that can be considered two individual joints: the meniscotemporal (suprameniscal) joint that enables translational movement, and the condylomeniscal (inframeniscal) joint that permits rotational movements. The articular surfaces comprise a hyaline/fibrocartilage composite with limited regenerative capacity. This joint structure is able to withstand the pressures occurring during mastication (Puricelli et al. 2012). Regenerative cell therapy is currently the focus of extensive research, mostly involving the use of stem cells of various origins. Embryogenic stem cells are impractical for ethical reasons, therefore, attention is shifting to the use of adult stem cells or so-called tissue-specific stem cells, such as adipose-derived stem cells (ADSCs). The ADSCs can differentiate into other cell types, including endothelial cells and other cells that participate in angiogenesis ACTA VET. BRNO 2019, 88: 49–56; https://doi.org/10.2754/avb201988010049 Address for correspondence: MUDr. Jan Štembírek, Ph.D. University Hospital Ostrava 17. listopadu 1790 708 52, Ostrava, Czech Republic E-mail: stembirek@iach.cz http://actavet.vfu.cz/ (Planat-Benard et al. 2004), as well as pancreatic endocrine cells that produce insulin, glucagon, and somatostatin (Timper et al. 2006). An in vitro study of rheumatoid arthritis reported that ADSCs exhibited immunomodulative effects, reducing the production of some proinflammatory cytokines and increasing production of the anti-inflammatory cytokine IL-10 and of antigen-specific regulatory T-lymphocytes (Gonzalez-Rey et al. 2010). However, the specific mechanisms underlying these processes remain unclear. The ADSCs can also accelerate neovascularisation. An investigation of skin healing in diabetic mice revealed that the ADSCs can increase expression of the vascular endothelial growth factor (VEGF) and the hypoxia-inducible factor 1-alpha (HIF-1α) (Miranville et al. 2004; Gao et al. 2011). Another promising therapeutic use of ADSCs is in the treatment of ischaemiacaused pathologies (Moon et al. 2006). Experiments using bioactive glass or β-tricalcium phosphate scaffolds seeded with autologous ADSCs have been conducted to examine the role of ADSCs in healing jaw and skull injuries. The authors reported successful integration of the construct with the surrounding skeleton in 10 of 13 cases (Sandor et al. 2014). While the stem cells’ immunomodulative character and influence on tissue healing can be beneficial in reconstructive surgery and healing of problematic wounds, there is also a cancerogenic potential. It was shown that ADSCs co-cultivated with cancer cells can increase their multiplying (Yu et al. 2008). Notably, in breast cancer, both local and intravenous administration of ADSCs reportedly induces tumour cell proliferation and increases the risk of metastases (Muehlberg et al. 2009). Studies have also described the use of undifferentiated xenogenous ADSCs in the rabbit, for treatment of neural tissue (Lasso et al. 2015) or osteochondral defects (Jang et al. 2014). In this study, we used a relatively cheap and ethically sourced heterogeneous population of cells from adipose tissue, termed human adipose-derived regenerative cells (ADRCs). These cells include ADSCs, endothelial cells, smooth muscle cells, haematopoietic cells, and other stromal cells. Compared to pure ADSCs, ADRCs are easier and less expensive to obtain, and are already used in clinical practise at our hospital. We used a rabbit model because this animal is easy to breed and is bigger than mice or rats, and thus more suitable for some types of studies, including investigations of the TMJ. The present study was designed to examine the suitability of direct application of unfiltered ADRCs in a rabbit model for TMJ research, as well as the effects of such xenogenous cells on the healing of TMJ defects. Materials and Methods Animals and immunosuppression Seventeen 10-month-old male outbred New Zealand White SPF rabbits (strain Crl:KBL) were obtained from Charles River Laboratories, Inc. (Wilmington, USA). These rabbits were individually housed in wiremesh cages at an animal care facility with controlled environmental conditions at the University of Veterinary and Pharmaceutical Sciences Brno, Czech Republic. The room temperature was maintained at 20–23 °C, with 40–55% relative humidity, and a 12-h light/dark cycle. The rabbits had free access to water, and were fed a complete pelleted diet and hay ad libitum. This study was performed in accordance with the ethical principles stated in the Declaration of Helsinki and approved by the Ethics Committee of the Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences Brno, approval No. 30307/2013-11. The animal housing, handling, and euthanasia were approved by the Branch Commission for Animal Welfare of the Ministry of Agriculture of the Czech Republic (project PP52-2013 UVPS). After a three-week acclimatization period, the 17 rabbits were randomly divided into two groups: 9 in the experimental group and 8 in the control group. Prior to surgery, immunosuppression was induced in all rabbits via intramuscular administration of 2 mg/kg dexamethasone sodium phosphate (Dexamed, Medochemie Ltd, Limassol, Cyprus) three times at 6-h intervals (Jeklova et al. 2008). After surgery, all rabbits were administered 2 mg/kg of dexamethasone sodium phosphate 15 times at 2-day intervals (Jeklova et al. 2008).

Author Listing： Barbora Putnová;Pavel Hurník;Vladimir Jekl;Dušan Žiak;Vladimír Machoň;M. Skoric;Jiří Stránský;Jan Štembírek

Volume： 88

Pages： 49-56

DOI： 10.2754/AVB201988010049

Language： English

Journal： Acta Veterinaria Brno

ACTA VETERINARIA BRNO

ACTA VET BRNO

影响因子：0.6

是否综述期刊：否

是否OA：是

是否预警：不在预警名单内

发行时间：1969

ISSN：0001-7213

发刊频率：Quarterly

收录数据库：SCIE/Scopus收录

出版国家/地区：CZECH REPUBLIC

出版社：University of Veterinary and Pharmaceutical Sciences

期刊介绍

ACTA VETERINARIA BRNO is a scientific journal of the University of Veterinary and Pharmaceutical Sciences in Brno, Czech Republic.The scientific journal Acta Veterinaria Brno is dedicated to the publication of original research findings and clinical observations in veterinary and biomedical sciences. Original scientific research articles reporting new and substantial contribution to veterinary science and original methods that have not been submitted for publication elsewhere are considered for publication. A written statement to this effect should accompany the manuscript, along with approval for publication by the author´s head of department. The authors bear full responsibility for the contents of their contribution. Book reviews are published, too.

《布尔诺兽医学报》（Acta Veterinaria Brno）是捷克共和国布尔诺兽医和制药科学大学的科学期刊，专门发表兽医和生物医学科学的原创研究成果和临床观察。报告对兽医科学有新的和实质性贡献的原始科学研究文章以及尚未在其他地方提交发表的原始方法将被考虑发表。手稿应附有一份书面声明，沿着附有作者所在部门负责人的出版批准。作者对其稿件内容承担全部责任。书评也出版了。

年发文量	53
国人发稿量	-
国人发文占比	0%
自引率	33.3%
平均录取率	容易
平均审稿周期	较慢,18-36周
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偏重研究方向	农林科学-兽医学
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