+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Potential beneficial effects of ixmyelocel-T in the treatment of atherosclerotic diseases

, : Potential beneficial effects of ixmyelocel-T in the treatment of atherosclerotic diseases. Stem Cell Research & Therapy 4(6): 135-135

Advanced atherosclerotic lesions are characterized by lipid accumulation, inflammation, and defective efferocytosis. An ideal therapy should address all aspects of this multifactorial disease. Ixmyelocel-T therapy, an expanded autologous multicellular therapy showing clinical promise in the treatment of diseases associated with advanced atherosclerosis, includes a novel population of M2-like macrophages. Here, we examine the macrophages of ixmyelocel-T and determine their ability to influx modified cholesterol in an atheroprotective manner, maintaining cholesterol homeostasis and preventing cellular dysfunction and death, ultimately promoting reverse cholesterol efflux. Approximately 50 ml of whole bone marrow was obtained from healthy donors and shipped overnight. Bone marrow mononuclear cells (BMMNCs) were produced by using density gradient separation and cultured for approximately 12 days to generate ixmyelocel-T. CD14+ cells were isolated from ixmyelocel-T via positive selection for analysis. Ixmyelocel-T and human leukemia monocyte (THP-1) cells were loaded with acetylated low-density lipoprotein (Ac-LDL) for analysis. Flow cytometry and immunofluorescence were used to examine Ac-LDL uptake, expression of cytokines was analyzed by enzyme-linked immunofluorescence assay (ELISA), and quantitative real-time PCR was used to analyze expression of cholesterol-transport genes. Both the in vitro cholesterol efflux assay and in vivo reverse cholesterol transport assay were used to examine cholesterol transport. Ixmyelocel-T macrophages take up acetylated low-density lipoprotein and express the scavenger receptors CD36 and scavenger receptor-B1 (SR-B1). Ixmyelocel-T did not become apoptotic or proinflammatory after lipid loading. The cholesterol transporter genes ABAC1 and ABCG1 were both statistically significantly upregulated when ixmyelocel-T macrophages were loaded with cholesterol. Ixmyelocel-T also exhibited enhanced apolipoprotein A-I (ApoAI)-mediated cholesterol efflux. In addition, in vivo reverse cholesterol-transport assay demonstrated that ixmyelocel-T was able to efflux cholesterol in this model. Ixmyelocel-T macrophages influx modified cholesterol, remained anti-inflammatory in the face of lipid loading and inflammatory challenge, and displayed enhanced cholesterol efflux capabilities. These combined features suggest that this autologous multicellular therapy may exert beneficial effects in atherosclerotic diseases.


PMID: 24405662

DOI: 10.1186/scrt346

Other references

Price; Harmin, 1992: Reply to "Comment on 'Differential equation for the spherical dipole matrix elements of hydrogen' ". Physical Review. A, Atomic, Molecular, and Optical Physics 46(9): 6110-6110

Gothot, A.; Pyatt, R.; Mcmahel, J.; Grigsby, S.; Srour, E.F., 1996: Activation and proliferation kinetics of single quiescent CD34+ cells residing in GO. Experimental Hematology (Charlottesville) 24(9): 1031

Noronha, M.; Dreiling, D.A.; Bordalo, O., 1978: The parotid and the pancreas part 4 parotid secretion after secretin stimulation as a screening test of pancreatic dys function. Salivary and pancreatic secretions were obtained simultaneously in patients, after secretin, in order to evaluate the usefulness of such data in the diagnosis of pancreatic disorders. Pancreatic pathology was associated with decreased salivary flo...

Michelis, F.V.; Petrogiannopoulos, C.L.; Papamichael, K.X.; Kostakos, N.D.; Kiagia, E.Z.; Deliousis, A.; Zacharof, A.K., 2008: Lymphomatous pericardial effusion positive for Mycobacterium tuberculosis by PCR analysis. International Journal of Infectious Diseases 12(5): 564-565

Anonymous, 1985: Rubella prevention in the United States. Bulletin of the Pan American Health Organization 19(4): 395-396

Kappes, U.P.; Ruenger, T.M., 2003: Contribution of pyrimidine dimers to UVA mutagenesis. Journal of Investigative Dermatology 121(1): 1130, July

Mohyeldin, A.; Lonser, R.R.; Elder, J.Bradley., 2016: Real-time magnetic resonance imaging-guided frameless stereotactic brain biopsy: technical note. The object of this study was to assess the feasibility, accuracy, and safety of real-time MRI-compatible frameless stereotactic brain biopsy. Clinical, imaging, and histological data in consecutive patients who underwent stereotactic brain biopsy...

DeBakey, L.; DeBakey, S., 1983: Syntactic orphans and adoptees: unattached participles. II. Medical misconstructions. International Journal of Cardiology 3(2): 231-236

Badecker, W.; Caramazza, A., 1987: The analysis of morphological errors in a case of acquired dyslexia. An issue that is persistently raised in studies of subjects who produce morphological errors in reading and other tasks is whether these errors are the consequence of a morphological processing deficit, or whether they in any way reflect morpholog...

Laude, Horton M., 1941: Combined effects of potassium supply and growth substances on plant development. Effects at different levels of K nutrition of indoleacetic acid and of [alpha] naphthalene acetamide, applied individually in a series of concs. in the nutrient soln. to red kidney beans (Phaseolus vulgaris) grown in sand culture in the greenhouse...