Gómez Martha C, Qin Qian, Biancardi Monica N, Galiguis Jason, Dumas Cherie, MacLean Robert A, Wang Guoshun, Pope C Earle
1 Audubon Center for Research of Endangered Species , New Orleans, LA, 70124.
2 Gene Therapy Program, Louisiana State University Health Sciences Center , New Orleans, LA, 70112.
Cell Reprogram. 2015 Oct;17(5):376-92. doi: 10.1089/cell.2015.0040. Epub 2015 Aug 28.
Transplantation of mesenchymal stem cells (MSCs) isolated from bone marrow or adipose tissue is emerging as a promising tool for cell replacement therapy and regenerative medicine in domestic and endangered animal species. Defining the differentiation capability of adipose-derived mesenchymal stromal/stem cells (AMSCs) collected from different depot sites of adipose tissue will be essential for developing strategies for cell replacement therapy. In the present study, we compared the biological characteristics of domestic cat AMSCs isolated from visceral fat of the abdominal cavity (AB) with AMSCs from subcutaneous (SQ) tissue, and the functional capability of domestic and black-footed cat (Felis nigripes) AMSCs to differentiate into other cell types. Our results showed that both domestic and black-footed cat adipose-derived stromal vascular fractions contained AMSCs. Both domestic cat AB- and SQ-AMSCs showed important clonogenic ability and the minimal MSC immunophenotype as defined by the International Society for Cellular Therapy in humans. However, domestic cat AB-AMSCs had higher percentages of cells positive for MSCs-associated cluster of differentiation (CD) markers CD90(+) and CD105(+) (92% and 80%, respectively) than those of SQ-AMSCs (77% and 58%, respectively). Although these results may suggest that AB-AMSCs may be more multipotent than SQ-AMSCs, both types of cells showed similar expression of pluripotent genes Oct-4 and Klf4, except for higher expression of Nanog than in AB-AMSCs, and equivalent in vitro multilineage differentiation. Under appropriate stimuli, the black-footed cat and both domestic cat AB- and SQ-AMSCs differentiated not only toward mesoderm cell lineages but also toward ectoderm cell lineage, such as neuron cell-like cells. Black-footed cat AMSCs had more capability to differentiate toward chondrocytes. These results suggest that the defined AMSC population (regardless of site of collection) could potentially be employed as a therapeutic agent for both domestic and endangered diseased or injured felids.
从骨髓或脂肪组织中分离的间充质干细胞（MSCs）移植，正成为一种有前景的工具，用于家畜和濒危动物物种的细胞替代疗法和再生医学。明确从脂肪组织不同储存部位收集的脂肪来源间充质基质/干细胞（AMSCs）的分化能力，对于制定细胞替代治疗策略至关重要。在本研究中，我们比较了从腹腔内脏脂肪（AB）分离的家猫AMSCs与皮下（SQ）组织来源的AMSCs的生物学特性，以及家猫和黑足猫（Felis nigripes）AMSCs向其他细胞类型分化的功能能力。我们的结果表明，家猫和黑足猫的脂肪来源基质血管成分中均含有AMSCs。家猫AB-AMSCs和SQ-AMSCs均表现出重要的克隆形成能力，以及符合国际细胞治疗协会定义的人类最小MSCs免疫表型。然而，家猫AB-AMSCs中与MSCs相关的分化簇（CD）标记CD90(+)和CD105(+)阳性细胞的百分比（分别为92%和80%）高于SQ-AMSCs（分别为77%和58%）。尽管这些结果可能表明AB-AMSCs比SQ-AMSCs具有更强的多能性，但两种类型的细胞均显示多能基因Oct-4和Klf4的表达相似，只是Nanog在SQ-AMSCs中的表达高于AB-AMSCs，且二者具有同等的体外多向分化能力。在适当刺激下，黑足猫以及家猫AB-和SQ-AMSCs不仅向中胚层细胞谱系分化，还向外胚层细胞谱系分化，如神经元样细胞。黑足猫AMSCs向软骨细胞分化的能力更强。这些结果表明，确定的AMSCs群体（无论收集部位如何）有可能被用作治疗家畜和濒危患病或受伤猫科动物的治疗剂。
