Library - Atherosclerosis
Stem Cells Int. 2015;2015:734731. doi: 10.1155/2015/734731. Epub 2015 Aug 2.
Stem Cells and Regenerative Medicine: Myth or Reality of the 21th Century.
Stoltz JF1, de Isla N2, Li YP3, Bensoussan D1, Zhang L4, Huselstein C2, Chen Y5, Decot V1, Magdalou J2, Li N6, Reppel L1, He Y3.
1CNRS, UMR 7365, Lorraine University, 54500 Vandoeuvre, France ; Nancy Hospital (CHU), Cell and Tissue Therapy Unit (UTCT), 54500 Vandoeuvre, France ; Lorraine University, 54000 Nancy, France.
2CNRS, UMR 7365, Lorraine University, 54500 Vandoeuvre, F rance ; Lorraine University, 54000 Nancy, France.
3Medical College and Zhongnan Hospital, Wuhan University, Wuhan, China.
4Service de Thérapie Cellulaire, Calmette Hospital, Kunming, China.
5Medical School, Wuhan University, Wuhan, Hubei, China.
6Anzhen Hospital, Cardiovascular and Lung Research Center, Beijing, China.
Since the 1960s and the therapeutic use of hematopoietic stem cells of bone marrow origin, there has been an increasing interest in the study of undifferentiated progenitors that have the ability to proliferate and differentiate into various tissues. Stem cells (SC) with different potency can be isolated and characterised. Despite the promise of embryonic stem cells, in many cases, adult or even fetal stem cells provide a more interesting approach for clinical applications. It is undeniable that mesenchymal stem cells (MSC) from bone marrow, adipose tissue, or Wharton’s Jelly are of potential interest for clinical applications in regenerative medicine because they are easily available without ethical problems for their uses. During the last 10 years, these multipotent cells have generated considerable interest and have particularly been shown to escape to allogeneic immune response and be capable of immunomodulatory activity. These properties may be of a great interest for regenerative medicine. Different clinical applications are under study (cardiac insufficiency, atherosclerosis, stroke, bone and cartilage deterioration, diabetes, urology, liver, ophthalmology, and organ’s reconstruction). This review focuses mainly on tissue and organ regeneration using SC and in particular MSC.
Stem Cells. 2012 May;30(5):1030-41. doi: 10.1002/stem.1047.
Adipose tissue-derived mesenchymal stem cells improve revascularization outcomes to restore renal function in swine atherosclerotic renal artery stenosis.
Eirin A1, Zhu XY, Krier JD, Tang H, Jordan KL, Grande JP, Lerman A, Textor SC, Lerman LO.
1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota 55905, USA.
Reno-protective strategies are needed to improve renal outcomes in patients with atherosclerotic renal artery stenosis (ARAS). Adipose tissue-derived mesenchymal stem cells (MSCs) can promote renal regeneration, but their potential for attenuating cellular injury and restoring kidney repair in ARAS has not been explored. We hypothesized that replenishment of MSC as an adjunct to percutaneous transluminal renal angioplasty (PTRA) would restore renal cellular integrity and improve renal function in ARAS pigs. Four groups of pigs (n = 7 each) were studied after 16 weeks of ARAS, ARAS 4 weeks after PTRA and stenting with or without adjunct intrarenal delivery of MSC (10 × 10(6) cells), and controls. Stenotic kidney blood flow (renal blood flow [RBF]) and glomerular filtration rate (GFR) were measured using multidetector computer tomography (CT). Renal microvascular architecture (micro-CT), fibrosis, inflammation, and oxidative stress were evaluated ex vivo. Four weeks after successful PTRA, mean arterial pressure fell to a similar level in all revascularized groups. Stenotic kidney GFR and RBF remained decreased in ARAS (p = .01 and p = .02) and ARAS + PTRA (p = .02 and p = .03) compared with normal but rose to normal levels in ARAS + PTRA + MSC (p = .34 and p = .46 vs. normal). Interstitial fibrosis, inflammation, microvascular rarefaction, and oxidative stress were attenuated only in PTRA + MSC-treated pigs. A single intrarenal delivery of MSC in conjunction with renal revascularization restored renal hemodynamics and function and decreased inflammation, apoptosis, oxidative stress, microvascular loss, and fibrosis. This study suggests a unique and novel therapeutic potential for MSC in restoring renal function when combined with PTRA in chronic experimental renovascular disease.
Keywords: renal artery stenosis, progenitor cells, renal hypertension, revascularization
Tissue Eng Part C Methods. 2011 Feb;17(2):145-54. doi: 10.1089/ten.TEC.2010.0139. Epub 2010 Oct 26.
Transplantation of human adipose tissue-derived multilineage progenitor cells reduces serum cholesterol in hyperlipidemic Watanabe rabbits.
Okura H1, Saga A, Fumimoto Y, Soeda M, Moriyama M, Moriyama H, Nagai K, Lee CM, Yamashita S, Ichinose A, Hayakawa T, Matsuyama A.
1Department of Somatic Stem Cell Therapy and Health Policy, Foundation for Biomedical Research and Innovation, Kobe, Japan.
Familial hypercholesterolemia (FH) is an autosomal codominant disease characterized by high concentrations of proatherogenic lipoproteins and premature atherosclerosis secondary to low-density lipoprotein (LDL) receptor deficiency. We examined a novel cell therapy strategy for the treatment of FH in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for homozygous FH. We delivered human adiposetissue-derived multilineage progenitor cells (hADMPCs) via portal vein and followed by immunosuppressive regimen to avoid xenogenic rejection. Transplantation of hADMPCs resulted in significant reductions in total cholesterol, and the reductions were observed within 4 weeks and maintained for 12 weeks. (125)I-LDL turnover study showed that the rate of LDL clearance was significantly higher in the WHHL rabbits with transplanted hADMPCs than those without transplanted. After transplantation hADMPCs were localized in the portal triad, subsequently integrated into the hepatic parenchyma. The integrated cells expressed human albumin, human alpha-1-antitrypsin, human Factor IX, human LDL receptors, and human bile salt export pump, indicating that the transplanted hADMPCs resided, survived, and showed hepatocytic differentiation in vivo and lowered serum cholesterol in the WHHL rabbits. These results suggested that hADMPC transplantation could correct the metabolic defects and be a novel therapy for inherited liver diseases.