Alternative therapies are currently being developed to treat patients with chronic limb ischemia who are unable to be revascularized in order to avoid amputation. Cell-based therapy using mononuclear cells is gaining attention as many clinical trials are currently underway. We review cell differentiation along with the different potential cell sources for use in therapeutic angiogenesis.
NorgrenL, HiattWR, DormandyJA. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II).J Vasc Surg2007; 45 (Suppl. S):S5-67
2.
RivardA, FabreJE, SilverM. Age-dependent impairment of angiogenesis.Circulation1999; 99: 111-20
3.
RajagopalanS, MohlerERIII, LedermanRJ. Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication.Circulation2003; 108: 1933-8
4.
Tateishi-YuyamaE, MatsubaraH, MuroharaT. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial.Lancet2002; 360: 427-35
5.
MiyamotoK, NishigamiK, NagayaN. Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans.Circulation2006; 114: 2679-84
6.
BartschT, BrehmM, ZeusT. Autologous mononuclear stem cell transplantation in patients with peripheral occlusive arterial disease.J Cardiovasc Nurs2006; 21: 430-2
7.
EsatoK, HamanoK, LiTS. Neovascularization induced by autologous bone marrow cell implantation in peripheral arterial disease.Cell Transplant2002; 11: 747-52
8.
HigashiY, KimuraM, HaraK. Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia.Circulation2004; 109: 1215-8
9.
MiyamotoM, YasutakeM, TakanoH. Therapeutic angiogenesis by autologous bone marrow cell implantation for refractory chronic peripheral arterial disease using assessment of neovascularization by 99mTc-tetrofosmin (TF) perfusion scintigraphy.Cell Transplant2004; 13: 429-37
10.
SaigawaT, KatoK, OzawaT. Clinical application of bone marrow implantation in patients with arteriosclerosis obliterans, and the association between efficacy and the number of implanted bone marrow cells.Circ J2004; 68: 1189-93
11.
DurduS, AkarAR, AratM. Autologous bone-marrow mononuclear cell implantation for patients with Rutherford grade II-III thromboangiitis obliterans.J Vasc Surg2006; 44: 732-9
12.
KajiguchiM, KondoT, IzawaH. Safety and efficacy of autologous progenitor cell transplantation for therapeutic angiogenesis in patients with critical limb ischemia.Circ J2007; 71: 196-201
13.
TillJE, McCE. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells.Radiat Res1961; 14: 213-22
14.
LorenzE, UphoffD, ReidTR. Modification of irradiation injury in mice and guinea pigs by bone marrow injections.J Natl Cancer Inst1951; 12: 197-201
15.
WuAM, TillJE, SiminovitchL. A cytological study of the capacity for differentiation of normal hemopoietic colony-forming cells.J Cell Physiol1967; 69: 177-84
16.
DickJE, MagliMC, HuszarD. Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice.Cell1985; 42: 71-9
17.
KellerG, PaigeC, GilboaE. Expression of a foreign gene in myeloid and lymphoid cells derived from multipotent haematopoietic precursors.Nature1985; 318: 149-54
18.
LemischkaIR, RauletDH, MulliganRC. Developmental potential and dynamic behavior of hematopoietic stem cells.Cell1986; 45: 917-27
19.
SmithLG, WeissmanIL, HeimfeldS. Clonal analysis of hematopoietic stem-cell differentiation in vivo. Proc Natl Acad Sci USA1991; 88: 2788-92
20.
OsawaM, HanadaK, HamadaH. Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell.Science1996; 273: 242-5
21.
KielMJ, YilmazOH, IwashitaT. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells.Cell2005; 121: 1109-21
22.
DykstraB, KentD, BowieM. Long-term propagation of distinct hematopoietic differentiation programs in vivo. Cell Stem Cell2007; 1: 218-29
23.
ManssonRZS, BryderD, SigvardssonM. The road to commitment: lineage restriction events in hematopoiesis. In: WickremaA, KeeB, eds. Molecular Basis of Hematopoiesis.New York: Springer, 2009: 23-46
24.
TavassoliM. Embryonic and fetal hemopoiesis: an overview.Blood Cells1991; 17: 269-81; discussion 282-6
25.
ZanjaniED, AscensaoJL, TavassoliM. Liver-derived fetal hematopoietic stem cells selectively and preferentially home to the fetal bone marrow.Blood1993; 81: 399-404
26.
McGrathKE, PalisJ. Hematopoiesis in the yolk sac: more than meets the eye.Exp Hematol2005; 33: 1021-8
27.
PietilaI, VainioS. The embryonic aorta-gonad-mesonephros region as a generator of haematopoietic stem cells.APMIS2005; 113: 804-12
28.
MorrisonSJ, UchidaN, WeissmanIL. The biology of hematopoietic stem cells.Annu Rev Cell Dev Biol1995; 11: 35-71
29.
OgawaM. Effects of hemopoietic growth factors on stem cells in vitro.Hematol Oncol Clin North Am1989; 3: 453-64
30.
OgawaM. Hemopoietic stem cells: stochastic differentiation and humoral control of proliferation.Environ Health Perspect1989; 80: 199-207
31.
GrafT. Differentiation plasticity of hematopoietic cells.Blood2002; 99: 3089-101
32.
AsaharaT, MuroharaT, SullivanA. Isolation of putative progenitor endothelial cells for angiogenesis.Science1997; 275: 964-7
33.
IsnerJM, AsaharaT. Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization.J Clin Invest1999; 103: 1231-6
34.
CarmelietP. Angiogenesis in health and disease.Nat Med2003; 9: 653-60
HelischA, SchaperW. Arteriogenesis: the development and growth of collateral arteries.Microcirculation2003; 10: 83-97
37.
CapiodJC, TournoisC, VitryF. Characterization and comparison of bone marrow and peripheral blood mononuclear cells used for cellular therapy in critical leg ischaemia: towards a new cellular product.Vox Sang2009; 96: 256-65
38.
HernandezP, CortinaL, ArtazaH. Autologous bone-marrow mononuclear cell implantation in patients with severe lower limb ischaemia: a comparison of using blood cell separator and Ficoll density gradient centrifugation.Atherosclerosis2007; 194: e52-6
39.
MagriD, VasilasP, MutoA. Elevated monocytes in patients with critical limb ischemia diminish after bypass surgery.J Surg Res2011; 167: 140-50
KawamuraA, HorieT, TsudaI. Clinical study of therapeutic angiogenesis by autologous peripheral blood stem cell (PBSC) transplantation in 92 patients with critically ischemic limbs.J Artif Organs2006; 9: 226-33
42.
IbaO, MatsubaraH, NozawaY. Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs.Circulation2002; 106: 2019-25
43.
LiS, ZhouB, HanZC. Therapeutic neovascularization by transplantation of mobilized peripheral blood mononuclear cells for limb ischemia. A comparison between CD34+ and CD34-mononuclear cells.Thromb Haemost2006; 95: 301-11
44.
KamihataH, MatsubaraH, NishiueT. Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines.Circulation2001; 104: 1046-52
45.
KocherAA, SchusterMD, SzabolcsMJ. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function.Nat Med2001; 7: 430-6
46.
HonoldJ, LehmannR, HeeschenC. Effects of granulocyte colony simulating factor on functional activities of endothelial progenitor cells in patients with chronic ischemic heart disease.Arterioscler Thromb Vasc Biol2006; 26: 2238-43
47.
ZhouB, LiuPX, LanHF. Enhancement of neovascularization with mobilized blood cells transplantation: supply of angioblasts and angiogenic cytokines.J Cell Biochem2007; 102: 183-95
48.
van FurthR, CohnZA. The origin and kinetics of mononuclear phagocytes.J Exp Med1968; 128: 415-35
49.
GeissmannF, ManzMG, JungS. Development of monocytes, macrophages, and dendritic cells.Science2010; 327: 656-61
50.
AuffrayC, SiewekeMH, GeissmannF. Blood monocytes: development, heterogeneity, and relationship with dendritic cells.Annu Rev Immunol2009; 27: 669-92
51.
AuffrayC, FoggD, GarfaM. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior.Science2007; 317: 666-70
52.
NahrendorfM, SwirskiFK, AikawaE. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions.J Exp Med2007; 204: 3037-47
53.
ArnoldL, HenryA, PoronF. Inflammatory monocytes recruited after skeletal muscle injury switch into anti-inflammatory macrophages to support myogenesis.J Exp Med2007; 204: 1057-69
54.
GehlingUM, ErgunS, SchumacherU. In vitro differentiation of endothelial cells from ACl33-positive progenitor cells.Blood2000; 95: 3106-12
55.
HristovM, WeberC. Endothelial progenitor cells: characterization, pathophysiology, and possible clinical relevance.J Cell Mol Med2004; 8: 498-508
56.
PeichevM, NaiyerAJ, PereiraD. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors.Blood2000; 95: 952-8
57.
NapoliC, HayashiT, CacciatoreF. Endothelial progenitor cells as therapeutic agents in the microcirculation: an update.Atherosclerosis2011; 215: 9-22
58.
ShantsilaE, WatsonT, TseHF. New insights on endothelial progenitor cell subpopulations and their angiogenic properties.J Am Coll Cardiol2008; 51: 669-71
59.
SievekingDP, BuckleA, CelermajerDS. Strikingly different angiogenic properties of endothelial progenitor cell subpopulations: insights from a novel human angiogenesis assay.J Am Coll Cardiol2008; 51: 660-8
60.
TimmermansF, Van HauwermeirenF, De SmedtM. Endothelial outgrowth cells are not derived from CD133+ cells or CD45+ hematopoietic precursors.Arterioscler Thromb Vasc Biol2007; 27: 1572-9
61.
AsaharaT, TakahashiT, MasudaH. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells.EMBO J1999; 18: 3964-72
62.
CarmelietP. Mechanisms of angiogenesis and arteriogenesis.Nat Med2000; 6: 389-95
63.
RehmanJ, LiJ, OrschellCM. Peripheral blood ‘endothelial progenitor cells’ are derived from monocyte/macrophages and secrete angiogenic growth factors.Circulation2003; 107: 1164-9
64.
BanfiA, von DegenfeldG, BlauHM. Critical role of microenvironmental factors in angiogenesis.Curr Atheroscler Rep2005; 7: 227-34
65.
FazelS, CiminiM, ChenL. Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines.J Clin Invest2006; 116: 1865-77
66.
TseHF, SiuCW, ZhuSG. Paracrine effects of direct intramyocardial implantation of bone marrow derived cells to enhance neovascularization in chronic ischaemic myocardium.Eur J Heart Fail2007; 9: 747-53
67.
AsaharaT, MasudaH, TakahashiT. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization.Circ Res1999; 85: 221-8
68.
KawamotoA, GwonHC, IwaguroH. Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia.Circulation2001; 103: 634-7
69.
LeoneAM, RutellaS, BonannoG. Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function.Eur Heart J2005; 26: 1196-204
70.
XuQ, ZhangZ, DavisonF. Circulating progenitor cells regenerate endothelium of vein graft atherosclerosis, which is diminished in ApoE-deficient mice.Circ Res2003; 93: e76-86
71.
LasalaGP, SilvaJA, GardnerPA. Combination stem cell therapy for the treatment of severe limb ischemia: safety and efficacy analysis.Angiology2010; 61: 551-6
72.
ChamberlainG, FoxJ, AshtonB. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing.Stem Cells2007; 25: 2739-49
73.
La RoccaG, AnzaloneR, CorraoS. Isolation and characterization of Oct-4+/HLA-G+ mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers.Histochem Cell Biol2009; 131: 267-82
74.
GojoS, GojoN, TakedaY. In vivo cardiovasculogenesis by direct injection of isolated adult mesenchymal stem cells.Exp Cell Res2003; 288: 51-9
75.
RookmaakerMB, VerhaarMC, LoomansCJ. CD34+ cells home, proliferate, and participate in capillary formation, and in combination with CD34– cells enhance tube formation in a 3-dimensional matrix.Arterioscler Thromb Vasc Biol2005; 25: 1843-50
UrbichC, HeeschenC, AicherA. Relevance of monocytic features for neovascularization capacity of circulating endothelial progenitor cells.Circulation2003; 108: 2511-6