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Intra-articular transplantation of porcine adipose-derived stem cells for the treatment of canine osteoarthritis: A pilot study

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World Journal of Transplantation 2014年第3期4卷 196-205页

作者： Shen-Yang Tsai Yun-Ching Huang Ling-Ling Chueh Lih-Seng Yeh Ching-Shwun Lin Institute of Veterinary Clinical Sciences School of Veterinary Medicine National Taiwan University Division of Urology Department of SurgeryChang Gung Memorial Hospital Graduate Institute of Veterinary Medicine School of Veterinary Medicine National Taiwan University Department of Urology School of MedicineUniversity of California San Francisco CA 94143-0738 United States

AIM: To test whether intra-articular injection of porcine adipose-derived stem cells(ADSCs) can treat canine osteoarthritis(OA).METHODS: To enroll in this study dogs must have stifle joint OA that had lasted ≥ 3 mo and been treated with OA medication without significant improvement. Three dogs fulfilled these criteria and were thus subjects for ADSCs treatment. ADSCs were isolated from abdominal adipose tissue of a 2-mo-old female Yorkshire pig. Their stem cell marker expression was examined by immunofluorescence staining. For treatment, 5 million ADSCs were injected into the diseased joint of each dog. In the next 48 h, the patient was observed for signs of inflammatory and allergic reactions. Thepatient was then discharged to the owner and, at 2, 6, and 12 wk, followed up with orthopedic assessment, owner questionnaire, X-ray imaging, and force-plate gait analysis.RESULTS: Porcine ADSCs expressed mesenchymal stem cell markers CD90 and CD105. Injection of porcine ADSCs into canine stifle joints did not cause any inflammatory or allergic reactions. Orthopedic evaluation found improvements in two dogs, particularly at the longest time point. Owners' evaluation found increased capacity and decreased pain in all three dogs' activities such as walking and running. Radiographic evaluation did not find statistically significant differences before and after treatment. Force-plate analysis found significant improvements in all three dogs after treatment.CONCLUSION: Xenotransplantation of ADSCs for the treatment of OA is feasible. Further studies are needed to validate this novel treatment modality, which can then be implemented for the routine treatment of OA in veterinary medicine.

关键词： Canine osteoarthritis adipose-derived stem cells Intra-articular transplantation Intra-articular injection Veterinary clinical study

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Advances in the research of basic study and clinical application of adipose-derived mesenchymal stem cells

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Discussion of Clinical Cases 2018年第1期5卷 36-42页

作者： Shengjun Cao Lingfeng Wang Te Ba Zhidong Rong Guolin Hu Biao Zhou Quan Li Department of Burns The Third Affiliated Hospital of Inner Mongolia Medical UniversityBaotouChina

Since the discovery of adipose-derived mesenchymal stem cell (ADSC) in more than ten years, a great progress has been made from its basic research to clinical application. Compared with bone marrow mesenchymal stem cells, ADSC is more abundant in reserve, easier to obtain with fewer injuries and less complications. These cells have multiple differentiation potential and can differentiate into adipocytes, chondrocytes and osteoblasts with the influence of different inducing factors. Early studies of ADSC mainly focused on the ability of multi-directional differentiation, especially on the regeneration of bone defects and cartilage tissue. At present, the researches mainly focus on immunoregulation and paracrine function of ADSC. Although ADSC has made a great progress in clinical application, the cell preparation, use pattern, and mechanisms in clinical treatment are not clear. This paper elaborates on these issues.

关键词： Stem cells adipose-derived stem cell Basic research Clinical application

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The Influence of Culture Medium Type on Cellular Phenotype of Canine adipose derived Stem Cells

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Open Journal of Regenerative Medicine 2014年第1期3卷 28-37页

作者： Kristina M. Kiefer G. Elizabeth Pluhar Michael G. Conzemius Timothy D. O’Brien Department of Veterinary Clinical Sciences College of Veterinary Medicine University of Minnesota St. Paul USA Department of Veterinary Population Medicine College of Veterinary Medicine University of Minnesota St. Paul USA

Canine adipose derived stem cells (ASCs) hold a great promise for the therapy of osteoarthritis in veterinary medicine. Current therapy is an autologous, stromal vascular fraction. Allogeneic ASCs provide many advantages, including efficient, cost-effective treatments while eliminating a surgical procedure in a diseased animal. Cultured ASCs can be expanded and characterized, allowing selection of desirable qualities. Use of allogeneic ASCs requires selection of a culture medium that provides consistent, desirable cellular products. The supplements within a medium can greatly influence cellular phenotypes. We hypothesized that medium type influenced cellular phenotype, allowing selection of a specified cellular product for clinical applications. We evaluated ASCs derived from adipose tissue of six dogs, assessing mRNA expression of proinflammatory: interleukin-1b, cyclooxygenase-2, and anti-inflammatory mediators: tissue inhibitor metalloproteinase-2 and interleukin -1 receptor antagonist, via quantitative RT-PCR prior to, and following culture in five cell culture media: basic cell growth medium (BGM), Keratinocyte N acetyl-L-cysteine supplemented (KNAC) medium, Multipotent Adult Progenitor Cell (MAPC) medium, serum free medium (SFM) and xeno-free medium. Major histocompatability complex I (MHCI), major histocompatability complex II (MHCII), CD44 and CD90 immunophenotypes were assessed via flow cytometry analysis. Tri-lineage differentiation (bone, adipose and cartilage tissue) was utilized to verify multipotency. SFM and xeno-free culture conditions did not produce cell expansion sufficient to assess phenotype. ASCs prior to culture had wide variability in all mediator levels, while culturing in the remaining conditions resulted in more predictable expression levels of inflammatory mediators, with a decrease in all levels. Cultured ASCs retained expression of cell surface markers MHCI, CD44 and CD90, while decreasing MHCII expression levels. KNAC and MAPC medium conditions consistently produced tri-lineage diff

关键词： Canine Mesenchymal Stem Cells adipose-derived Stromal Cells Culture Conditions

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adipose-derived stem cells in cutaneous wound repair

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Plastic and Aesthetic Research 2018年第8期5卷 16-23页

作者： Bong-Sung Kim Berthold Debye Justus P.Beier Department of Plastic Surgery Hand Surgery-Burn CenterUniversity Hospital RWTH AachenAachen 52074Germany

Growing interest in regenerative medicine and advances in adipose tissue research have led to the identification of mesenchymal stem cells in adipose tissue, so called adipose tissue-derived stem cells (ASCs). Due to the simple and safe harvest technique as well as high regenerative capacity, ASCs are regarded as a potential source for various indications including cutaneous wound repair. This review provides a short overview over mechanisms of ASC action in cutaneous wound repair and data regarding its clinical application. Mostly experimental data provide accruing evidence for the supportive effect of ASCs in cutaneous wound healing by secretion of soluble factors, differentiation into keratinocyte and fibroblasts, neovascularization and interaction with myofibroblasts. A number of in vivo experiments also support a positive effect of ASCs in different wound healing models. Furthermore, first clinical data evaluated the feasibility of ASCs in the treatment of different wound healing pathologies, e.g., chronic ulcers and burn wounds. Although the majority of currently available data indicate a beneficial role of ASCs in cutaneous wound repair, additional detailed experimental studies and larger, high-quality clinical trials are required to provide a reliable statement on the true value of ASCs in this context.

关键词： Cutaneous wound healing adipose-derived stem cells fat grafting regenerative medicine cell-based therapy

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adipose-derived stem cell therapy for severe muscle tears in working German shepherds: Two case reports

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Stem Cell Discovery 2012年第2期2卷 41-44页

作者： S. Gary Brown Robert J. Harman Linda L. Black Surgeon Veterinary Orthopedic and Surgery Service Clinical Professor of Veterinary Medicine Western University of Health Sciences Pomona USA Vet-Stem Inc. Poway USA

Injuries to muscle in the elite athlete are common and may be responsible for prolonged periods of loss of competitive activity. The implications for the athlete, his/her coach and team may be catastrophic if the injury occurs at a critical time in the athlete's diary. Imaging now plays a crucial role in diagnosis, prognostication and management of athletes with muscle injuries. This article discusses the methods available to clinicians and radiologists that are used to assess skeletal muscle injury. The spectrum of muscle injuries sustained in the elite athlete population is both discussed and illustrated.

关键词： adipose-derived Stem Cell Dog Muscle

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Human adipose tissue-derived stem cells in breast reconstruction following surgery for cancer: A controversial issue

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Stem Cell Discovery 2013年第3期3卷 164-166页

作者： Maria Giovanna Scioli Valerio Cervelli Pietro Gentile Alessandra Bielli Roberto Bellini Augusto Orlandi Anatomic Pathology Department of Biomedicine and Prevention Tor Vergata University Rome Italy

Breast cancer is the most common cancer in women. Patients, in particular young women, after surgical removal of the tumor have a poorer quality of life and psychological problems. Plastic surgery procedures for breast reconstruction, including autologous fat grafting, concur to reduce cosmetic and psychological problems. The maintenance of the transplanted fat is partially due to the presence of resident adipose derived-stem cells (ASCs). The latter can be isolated by digestion and centrifugation from the stromal vascular fraction (SVF) of subcutaneous adipose tissue. Intraoperatory SVF/ASC enrichment has been proposed to stabilize and optimalize autologous fat engraftment for breast reconstructive surgery after mastectomy, but the safety of these procedures is still uncertain. Although the literature offers contrasting opinions concerning the effects of ASCs on cancer growth according to the tumor type, at the present time ASC implementation for regenerative medicine therapies should be carefully considered in patients previously treated for breast cancer. At the present, reconstructive therapy utilizing ASC-enriched fat grafting should be postponed until there is no evidence of active disease.

关键词： Human adipose-derived Stem Cells Breast Cancer Breast Reconstruction Fat Grafting

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Encapsulated three-dimensional bioprinted structure seeded with urothelial cells:a new construction technique for tissue-engineered urinary tract patch

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Chinese Medical Journal 2020年第4期133卷 424-434页

作者： Yi-Peng Jin Chong Shi Yuan-Yi Wu Ji-Lei Sun Jiang-Ping Gao Yong Yang Department of Urology Sixth Medical Center of Chinese People's Liberation Army General HospitalBeijing 100048China The First Center of Department of Hepatobiliary Surgery Fifth Medical Center of Chinese People's Liberation Army General HospitalBeijing 100039China Department of Urology Fourth Medical Center of Chinese People's Liberation Army General HospitalBeijing 100048China Department of Urology First Medical Center of Chinese People's Liberation Army General HospitalBeijing 100853China

Background:Traditional tissue engineering methods to fabricate urinary tract patch have some drawbacks such as compromised cell viability and uneven cell distribution within scaffold.In this study,we combined three-dimensional(3D)bioprinting and tissue engineering method to form a tissue-engineered urinary tract patch,which could be employed for the application on Beagles urinary tract defect mode to verify its effectiveness on urinary tract reconstruction.Methods:Human adipose-derived stem cells(hADSCs)were dropped into smooth muscle differentiation medium to generate induced microtissues(ID-MTs),flow cytometry was utilized to detect the positive percentage for CD44,CD105,CD45,and CD34 of hADSCs.Expression of vascular endothelial growth factor A(VEGFA)and tumor necrosis factor-stimulated gene-6(TSG-6)in hADSCs and MTs were identified by Western blotting.Then the ID-MTs were employed for 3D bioprinting.The bioprinted structure was encapsulated by transplantation into the subcutaneous tissue of nude mice for 1 week.After retrieval of the encapsulated structure,hematoxylin and eosin and Masson’s trichrome staining were performed to demonstrate the morphology and reveal collagen and smooth muscle fibers,integral optical density(IOD)and area of interest were calculated for further semiquantitative analysis.Immunofluorescent double staining of CD31 andα-smooth muscle actin(α-SMA)were used to reveal vascularization of the encapsulated structure.Immunohistochemistry was performed to evaluate the expression of interleukin-2(IL-2),α-SMA,and smoothelin of the MTs in the implanted structure.Afterward,the encapsulated structure was seeded with human urothelial cells.Immunofluorescent staining of cytokeratins AE1/AE3 was applied to inspect the morphology of seeded encapsulated structure.Results:The semi-quantitative assay showed that the relative protein expression of VEGFA was 0.355±0.038 in the hADSCs vs.0.649±0.150 in the MTs(t=3.291,P=0.030),while TSG-6 expression was 0.492±0.092 in the hADSCs vs.1.256±0.401 in the MTs(t=

关键词： Human adipose-derived stem cells Urinary tract patch Microtissues Tissue engineering Three-dimensional bioprinting

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The neck burn scar contracture:a concept of effective treatment

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Burns & Trauma 2017年第3期5卷 140-147页

作者： Sadanori Akita Kenji Hayashida Satoshi Takaki Yoshihisa Kawakami Takuto Oyama Hiroyuki Ohjimi Department of Plastic Surgery Wound Repair and Regeneration School of Medicine Fukuoka University 7-45-1 Nanakuma Jonan ku Fukuoka 8140180 Japan Section of Plastic Surgery School of Medicine Shimane University Shimane Japan Department of Plastic Surgery School of Medicine Fukuoka University Fukuoka Japan

A neck scar contracture can severely and negatively affect the function of mastication, phonic, or breathing and result in neck pain and issues with esthetics. The best way is of course to avoid such contracture by means of non-surgical treatment such as use of a growth factor. The basic fibroblastic growth factor is clinically well proven in decreasing scar formation and improving healing. There are numerous reconstructive methods for neck contracture, especially when the lesions are relatively limited in part of the neck. However, a very severe and full circumferential scar contracture requires extensive reconstruction. The thin groin flap is one of the answers and well matches with the tissue texture and maintains the flexibility. Even with extensive burns and delayed reconstructions due to resuscitation first, the groin area is well preserved and can be safely harvested by dual vasculature systems of the superficial circumflex iliac artery and superficial epigastric artery, which warrant more reliability compared to the perforator flaps in this area. More demanding and stringent forms of the neck burn scar contracture are the sequelae of radiation. A radiation burn or radiation injury can be progressing and hard to heal. adipose-derived stem cells can reverse the scar contracture as the surrounding tissue is softened and can accelerate wound healing. In this review, different types of neck burn scar contracture and reconstructive methods are summarized, including innovative use of bFGF and ADSCs in the management of difficult wound healing and scar contracture.

关键词： Neck scar contracture Anatomical locations Prophylaxis Severe scar contracture Thin groin flap Radiation injury adipose-derived stem cell

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Stem cell therapy for the treatment of Leydig cell dysfunction in primary hypogonadism

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World Journal of Stem Cells 2016年第10期8卷 306-315页

作者： Taylor C Peak Nora M Haney William Wang Kenneth J DeLay Wayne J Hellstrom Department of Urology School of MedicineTulane University

The production of testosterone occurs within the Leydig cells of the testes. When production fails at this level from either congenital, acquired, or systemic disorders,the result is primary hypogonadism. While numerous testosterone formulations have been developed, none are yet fully capable of replicating the physiological patterns of testosterone secretion. Multiple stem cell therapies to restore androgenic function of the testes are under investigation. Leydig cells derived from bone marrow, adipose tissue, umbilical cord, and the testes have shown promise for future therapy for primary hypogonadism. In particular, the discovery and utilization of a group of progenitor stem cells within the testes, known as stem Leydig cells(SLCs), has led not only to a better understanding of testicular development, but of treatment as well. When combining this with an understanding of the mechanisms that lead to Leydig cell dysfunction, researchers and physicians will be able to develop stem cell therapies that target the specific step in the steroidogenic process that is deficient. The current preclinical studies highlight the complex nature of regenerating this steroidogenic process and the problems remain unresolved. In summary, there appears to be two current directions for stem cell therapy in male primary hypogonadism. The first method involves differentiating adult Leydig cells from stem cells of various origins from bone marrow, adipose, or embryonic sources. The second method involves isolating, identifying, and transplanting stem Leydig cells into testicular tissue. Theoretically, in-vivo re-activation of SLCs in men with primary hypogonadism due to age would be another alternative method to treat hypogonadism while eliminating the need for transplantation.

关键词： Stem cell therapy Leydig cells Primary hypogonadism Stem Leydig cells Testosterone Bone marrow-derived stem cells adipose-derived mesenchymal stem cells

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Current applications of adipose-derived stem cells and their future perspectives

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World Journal of Stem Cells 2014年第1期6卷 65-68页

作者： Eun-Hee Kim Chan Yeong Heo Department of Plastic and Reconstructive Surgery Seoul National University Bundang Hospital Department of Plastic and Reconstructive Surgery College of MedicineSeoul National University

Adult stem cells have a great potential to treat various diseases. For these cell-based therapies, adipose-derived stem cells(ADSCs) are one of the most promising stem cell types, including embryonic stem cells(ESCs) and induced pluripotent stem cells(iPSCs). ESCs and iPSCs have taken center stage due to their pluripotency. However, ESCs and iPSCs have limitations in ethical issues and in identification of characteristics, respectively. Unlike ESCs and iPSCs, ADSCs do not have such limitations and are not only easily obtained but also uniquely expandable. ADSCs can differentiate into adipocytes, osteoblasts, chondrocytes, myocytes and neurons under specific differentiation conditions, and these kinds of differentiation potential of ADSCs could be applied in regenerative medicine e.g., skin reconstruction, bone and cartilage formation, etc. In this review, the current status of ADSC isolation, differentiation and their therapeutic applications are discussed.

关键词： adipose-derived stem cells Isolation Differentiation Transplantation Cell-based therapy

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