scholarly journals Equine Hoof Stem Progenitor Cells (HPC) CD29 + /Nestin + /K15 + – a Novel Dermal/epidermal Stem Cell Population With a Potential Critical Role for Laminitis Treatment

Author(s):  
Krzysztof Marycz ◽  
Ariadna Pielok ◽  
Katarzyna Kornicka-Garbowska

AbstractLaminitis is a life threating, extremely painful and frequently recurrent disease of horses which affects hoof structure. It results from the disruption of blood flow to the laminae, contributing to laminitis and in severe separation of bone from the hoof capsule. Still, the pathophysiology of the disease remains unclear, mainly due to its complexity. In the light of the presented data, in the extremally difficult process of tissue structure restoration after disruption, a novel type of progenitor cells may be involved. Herein, we isolated and performed the initial characterization of stem progenitor cells isolated from the coronary corium of the equine feet (HPC). Phenotype of the cells was investigated with flow cytometry and RT-qPCR revealing the presence of nestin, CD29, and expression of progenitor cell markers including SOX2, OCT4, NANOG and K14. Morphology of HPC was investigated with light, confocal and SEM microscopes. Cultured cells were characterised by spindle shaped morphology, eccentric nuclei, elongated mitochondria, and high proliferation rate. Plasticity and multilineage differentiation potential was confirmed by specific staining and gene expression analysis. We conclude that HPC exhibit in vitro expansion and plasticity similar to mesenchymal stem cells, which can be isolated from the equine foot, and may be directly involved in the pathogenesis and recovery of laminitis. Obtained results are of importance to the field of laminitis treatment as determining the repairing cell populations could contribute to the discovery of novel therapeutic targets and agents including and cell‐based therapies for affected animals.

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Gokulakrishnan Iyer ◽  
Michael E Davis

Cardiac diseases are the leading causes of death throughout the world and transplantation of endogenous myocardial progenitor population with robust cardiovascular lineage differentiation potential is a promising therapeutic strategy. Therefore, in vitro expansion and transplantation of cardiac progenitor cells (CPCs) is currently in early clinical testing as a potential treatment for severe cardiac dysfunction. However, poor survival and engraftment of cells is one of the major limitations of cell transplantation therapy. Oxidative stress is increased in the ischemic myocardium and indirect inferences suggest the vulnerability of CPCs to oxidative stress. In this study, we show that in vitro, resident c-kit positive CPCs isolated from rat myocardium are significantly (p<0.05) resistant to superoxide-induced apoptosis compared to cardiomyocytes as analyzed by the number of sub-G1 population following xanthine/xanthine oxidase treatment. Interestingly, CPCs have two to four fold higher basal SOD1 and SOD2 activities (p<0.01) compared to cardiomyocytes and endothelial cells. Superoxide treatment increased expression of SOD1 (p<0.01), SOD2 (p<0.01), and glutathione peroxidase (p<0.05) mRNAs within 6 h of treatment compared to control cells. Recent studies suggest the involvement of AKT in controlling cell death, survival and also expression of SOD enzymes. Therefore, we investigated the involvement of AKT in CPCs subjected to oxidative stress. Western blot analysis revealed that the amount of phosphorylated AKT increased significantly within 10 minutes of xanthine/xanthine oxidase treatment. In addition, treatment with LY294002 - a PI3 kinase/AKT inhibitor, increased apoptosis in CPCs treated with superoxide. Our studies demonstrate a novel finding in which resident progenitor cells are protected from oxidative injury by containing higher basal levels of antioxidants as compared to myocytes. Moreover, under oxidant challenge antioxidant levels are regulated, possibly in an AKT-dependent manner. Further elucidation of this pathway may lead to novel therapeutic opportunities.


2019 ◽  
Vol 28 (11) ◽  
pp. 1404-1419
Author(s):  
Roger Esteban-Vives ◽  
Jenny Ziembicki ◽  
Myung Sun Choi ◽  
R. L. Thompson ◽  
Eva Schmelzer ◽  
...  

Various cell-based therapies are in development to address chronic and acute skin wound healing, for example for burns and trauma patients. An off-the-shelf source of allogeneic dermal cells could be beneficial for innovative therapies accelerating the healing in extensive wounds where the availability of a patient’s own cells is limited. Human fetal-derived dermal fibroblasts (hFDFs) show high in vitro division rates, exhibit low immunological rejection properties, and present scarless wound healing in the fetus, and previous studies on human fetal tissue-derived cell therapies have shown promising results on tissue repair. However, little is known about cell lineage stability and cell differentiation during the cell expansion process, required for any potential therapeutic use. We describe an isolation method, characterize a population, and investigate its potential for cell banking and thus suitability as a potential product for cell grafting therapies. Our results show hFDFs and a bone marrow-derived mesenchymal stem cell (BM-MSC) line shared identification markers and in vitro multilineage differentiation potential into osteogenic, chondrogenic, and adipogenic lineages. The hFDF population exhibited similar cell characteristics as BM-MSCs while producing lower pro-inflammatory cytokine IL-6 levels and higher levels of the wound healing factor hepatocyte growth factor. We demonstrate in vitro differentiation of hFDFs, which may be a problem in maintaining long-term lineage stability, potentially limiting their use for cell banking and therapy development.


2019 ◽  
pp. 019262331988046
Author(s):  
Qingqiu Yang ◽  
Mandi J Lopez

The equine hoof capsule, composed of modified epidermis and dermis, is vital for protecting the third phalanx from forces of locomotion. There are descriptions of laminitis, defined as inflammation of sensitive hoof tissues but recognized as pathologic changes with or without inflammatory mediators, in the earliest records of domesticated horses. Laminitis can range from mild to serious, and signs can be acute, chronic, or transition from acute, severe inflammation to permanently abnormal tissue. Damage within the intricate dermal and epidermal connections of the primary and secondary lamellae is often associated with lifelong changes in hoof growth, repair, and conformation. Decades of research contribute to contemporary standards of care that include systemic and local therapies as well as mechanical hoof support. Despite this, consistent mechanisms to restore healthy tissue formation following a laminitic insult are lacking. Endogenous and exogenous progenitor cell contributions to healthy tissue formation is established for most tissues. There is comparably little information about equine hoof progenitor cells. Equine hoof anatomy, laminitis, and progenitor cells are covered in this review. The potential of progenitor cells to advance in vitro equine hoof tissue models and translate to clinical therapies may significantly improve prevention and treatment of a devastating condition that has afflicted equine companions throughout history.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Hoda El-Kehdy ◽  
Guillaume Pourcher ◽  
Wenwei Zhang ◽  
Zahia Hamidouche ◽  
Sylvie Goulinet-Mainot ◽  
...  

In line with the search of effective stem cell population that would progress liver cell therapy and because the rate and differentiation potential of mesenchymal stem cells (MSC) decreases with age, the current study investigates the hepatogenic differentiation potential of human fetal liver MSCs (FL-MSCs). After isolation from 11-12 gestational weeks’ human fetal livers, FL-MSCs were shown to express characteristic markers such as CD73, CD90, and CD146 and to display adipocytic and osteoblastic differentiation potential. Thereafter, we explored their hepatocytic differentiation potential using the hepatogenic protocol applied for adult human liver mesenchymal cells. FL-MSCs differentiated in this way displayed significant features of hepatocyte-like cells as demonstratedin vitroby the upregulated expression of specific hepatocytic markers and the induction of metabolic functions including CYP3A4 activity, indocyanine green uptake/release, and glucose 6-phosphatase activity. Following transplantation, naive and differentiated FL-MSC were engrafted into the hepatic parenchyma of newborn immunodeficient mice and differentiatedin situ. Hence, FL-MSCs appeared to be interesting candidates to investigate the liver development at the mesenchymal compartment level. Standardization of their isolation, expansion, and differentiation may also support their use for liver cell-based therapy development.


1999 ◽  
Vol 158 (2) ◽  
pp. 265-278 ◽  
Author(s):  
Melissa K. Carpenter ◽  
Xia Cui ◽  
Zhong-yi Hu ◽  
Jennifer Jackson ◽  
Sandy Sherman ◽  
...  

Blood ◽  
2003 ◽  
Vol 102 (13) ◽  
pp. 4369-4376 ◽  
Author(s):  
James C. Mulloy ◽  
Jorg Cammenga ◽  
Francisco J. Berguido ◽  
Kaida Wu ◽  
Ping Zhou ◽  
...  

AbstractHematopoiesis is a complex process involving hematopoietic stem cell (HSC) self-renewal and lineage commitment decisions that must continue throughout life. Establishing a reproducible technique that allows for the long-term ex vivo expansion of human HSCs and maintains self-renewal and multipotential differentiation will allow us to better understand these processes, and we report the ability of the leukemia-associated AML1-ETO fusion protein to establish such a system. AML1-ETO-transduced human CD34+ hematopoietic cells routinely proliferate in liquid culture for more than 7 months, remain cytokine dependent for survival and proliferation, and demonstrate self-renewal of immature cells that retain both lymphoid and myeloid potential in vitro. These cells continue to express the CD34 cell surface marker and have ongoing telomerase activity with maintenance of telomere ends, however they do not cause leukemia in nonobese diabetic-severe combined immunodeficiency (NOD/SCID) mice. Identification of the signaling pathways that are modulated by AML1-ETO and lead to the self-renewal of immature human progenitor cells may assist in identifying compounds that can efficiently expand human stem and progenitor cells ex vivo. (Blood. 2003; 102:4369-4376)


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