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人脂肪来源干细胞在异种移植大鼠各器官中的器官特异性分化:一项初步研究。

Organ-Specific Differentiation of Human Adipose-Derived Stem Cells in Various Organs of Xenotransplanted Rats: A Pilot Study.

作者信息

Park Jung Ho, Choi Yeon Ju, Kang So Young, Ju Hyunjeong, Min Kyueng-Whan, Kim Nan Young, Park Ha Young, Kim Eun Soo, Kwon Mi Jung, Suh Yong Joon

机构信息

Department of Breast and Endocrine Surgery, Hallym University Sacred Heart Hospital, Anyang 14068, Korea.

Research Cooperation Center, Hallym University, Anyang 14068, Korea.

出版信息

Life (Basel). 2022 Jul 25;12(8):1116. doi: 10.3390/life12081116.

Abstract

Adipose-derived stem cells (ADSCs) are potential therapeutics considering their self-renewal capacity and ability to differentiate into all somatic cell types in vitro. The ideal ADSC-based therapy is a direct injection into the relevant organs. The objective of this study was to investigate the viability and safety of intra-organ human ADSC (h-ADSC) xenotransplants in vivo. Subcutaneous adipose tissue from the abdominal area of 10 patients was sampled. h-ADSCs were isolated from adipose tissue samples and identified using immunofluorescence antibodies. Multi-differentiation potential assays for adipocytes, osteocytes, and chondrocytes were performed. Cultured h-ADSCs at passage 4 were transplanted into multiple organs of 17 rats, including the skin, subcutaneous layer, liver, kidney, pancreas, and spleen. The h-ADSC-injected organs excised after 100 days were examined, and the survival of h-ADSCs was measured by quantitative real-time polymerase chain reaction (qRT-PCR) using specific human and rat target genes. h-ADSCs confirmed by stem cell phenotyping were induced to differentiate into adipogenic, osteogenic, and chondrogenic lineages in vitro. All rats were healthy and exhibited no side effects during the study; the transplanted h-ADSCs did not cause inflammation and were indiscernible from the native organ cells. The presence of transplanted h-ADSCs was confirmed using qRT-PCR. However, the engrafted survival rates varied as follows: subcutaneous fat (70.6%), followed by the liver (52.9%), pancreas (50.0%), kidney (29.4%), skin (29.4%), and spleen (12.5%). h-ADSCs were successfully transplanted into a rat model, with different survival rates depending on the organ.

摘要

脂肪来源干细胞(ADSCs)因其自我更新能力以及在体外分化为所有体细胞类型的能力,而成为潜在的治疗手段。理想的基于ADSCs的治疗方法是直接注射到相关器官中。本研究的目的是调查体内器官内人ADSCs(h-ADSCs)异种移植的生存能力和安全性。采集了10名患者腹部区域的皮下脂肪组织。从脂肪组织样本中分离出h-ADSCs,并使用免疫荧光抗体进行鉴定。对脂肪细胞、骨细胞和软骨细胞进行了多向分化潜能分析。将第4代培养的h-ADSCs移植到17只大鼠的多个器官中,包括皮肤、皮下层、肝脏、肾脏、胰腺和脾脏。在100天后切除注射了h-ADSCs的器官,并使用特异性人类和大鼠靶基因通过定量实时聚合酶链反应(qRT-PCR)测量h-ADSCs的存活情况。经干细胞表型鉴定确认的h-ADSCs在体外被诱导分化为脂肪生成、骨生成和软骨生成谱系。在研究过程中,所有大鼠均健康且未表现出副作用;移植的h-ADSCs未引起炎症,与天然器官细胞难以区分。使用qRT-PCR确认了移植的h-ADSCs的存在。然而,移植后的存活率各不相同,具体如下:皮下脂肪(70.6%),其次是肝脏(52.9%)、胰腺(50.0%)、肾脏(29.4%)、皮肤(29.4%)和脾脏(12.5%)。h-ADSCs成功移植到大鼠模型中,不同器官的存活率不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2146/9330795/4fc10bb783b3/life-12-01116-g001.jpg

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