The potential of cord blood stem cells for use in regenerative medicine

It is estimated that up to 128 million individuals might benefit from regenerative medicine therapy, or almost 1 in 3 individuals in the US. If accurate, the need to relieve suffering and reduce healthcare costs is an enormous motivator to rapidly bring stem cell therapies to the clinic. Unfortunately, embryonic stem (ES) cell therapies are limited at present by ethical and political constraints and, most importantly, by significant biologic hurdles. Thus, for the foreseeable future, the march of regenerative medicine to the clinic will depend on the development of non-ES cell therapies. At present, non-ES cells easily available in large numbers can be found in the bone marrow, adipose tissue and umbilical cord blood (CB). Each of these stem cells is being used to treat a variety of diseases. This review shows that CB contains multiple populations of pluripotent stem cells, and can be considered the best alternative to ES cells. CB stem cells are capable of giving rise to hematopoietic, epithelial, endothelial and neural tissues both in vitro and in vivo. Thus, CB stem cells are amenable to treat a wide variety of diseases including cardiovascular, ophthalmic, orthopedic, neurologic and endocrine diseases.

[1]  T. Murohara Therapeutic vasculogenesis using human cord blood-derived endothelial progenitors. , 2001, Trends in cardiovascular medicine.

[2]  A. Reddi,et al.  Effect of human umbilical cord blood cells on glycemia and insulitis in type 1 diabetic mice. , 2004, Biochemical and biophysical research communications.

[3]  H. Dinse,et al.  Spastic Paresis After Perinatal Brain Damage in Rats Is Reduced by Human Cord Blood Mononuclear Cells , 2006, Pediatric Research.

[4]  Nan Ma,et al.  Human cord blood cells induce angiogenesis following myocardial infarction in NOD/scid-mice. , 2005, Cardiovascular research.

[5]  Ralf Sodian,et al.  Living, autologous pulmonary artery conduits tissue engineered from human umbilical cord cells. , 2002, The Annals of thoracic surgery.

[6]  J. Sweetenham,et al.  Endothelial cell precursors are normal components of human umbilical cord blood , 1997, British journal of haematology.

[7]  M. Gaballa,et al.  Do adult stem cells ameliorate the damaged myocardium? Human cord blood as a potential source of stem cells. , 2007, Current vascular pharmacology.

[8]  G. Stassi,et al.  Heart infarct in NOD‐SCID mice: Therapeutic vasculogenesis by transplantation of human CD34+ cells and low dose CD34+KDR+ cells , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[9]  Shigeyuki Wakitani,et al.  Autologous Bone Marrow Stromal Cell Transplantation for Repair of Full-Thickness Articular Cartilage Defects in Human Patellae: Two Case Reports , 2004, Cell transplantation.

[10]  J. C. Nichols,et al.  Regenerative medicine of the eye: A short review , 2008 .

[11]  M. Laughlin,et al.  UC blood hematopoietic stem cells and therapeutic angiogenesis. , 2007, Cytotherapy.

[12]  Zhifeng Xiao,et al.  Reconstruction of Chemically Burned Rat Corneal Surface by Bone Marrow–Derived Human Mesenchymal Stem Cells , 2006, Stem cells.

[13]  S. Hoerstrup,et al.  Living patches engineered from human umbilical cord derived fibroblasts and endothelial progenitor cells. , 2005, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[14]  M. Pesce,et al.  Myoendothelial Differentiation of Human Umbilical Cord Blood–Derived Stem Cells in Ischemic Limb Tissues , 2003 .

[15]  M. Foss,et al.  Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. , 2009, JAMA.

[16]  P. Sanberg,et al.  Human umbilical cord blood stem cells infusion in spinal cord injury: engraftment and beneficial influence on behavior. , 2003, Journal of hematotherapy & stem cell research.

[17]  W. Low,et al.  Infusion of Human Umbilical Cord Blood Ameliorates Neurologic Deficits in Rats with Hemorrhagic Brain Injury , 2005, Annals of the New York Academy of Sciences.

[18]  Jingqiu Cheng,et al.  [Bone marrow mesenchymal stem cells: progress in bone/cartilage defect repair]. , 2002, Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi.

[19]  Yang Zeng,et al.  Differentiation of human umbilical cord blood stem cells into hepatocytes in vivo and in vitro. , 2006, World journal of gastroenterology.

[20]  P. Quesenberry,et al.  Participation of bone marrow derived cells in cutaneous wound healing , 2003, Journal of cellular physiology.

[21]  D. McKenna,et al.  Differentiation of umbilical cord blood-derived multilineage progenitor cells into respiratory epithelial cells. , 2006, Cytotherapy.

[22]  Patrick Carrier,et al.  Can we produce a human corneal equivalent by tissue engineering? , 2000, Progress in Retinal and Eye Research.

[23]  S. Hoerstrup,et al.  Umbilical cord blood derived endothelial progenitor cells for tissue engineering of vascular grafts. , 2004, The Annals of thoracic surgery.

[24]  N. Ende,et al.  Parkinson's disease mice and human umbilical cord blood. , 2002, Journal of medicine.

[25]  N. Forraz,et al.  Umbilical cord blood stem cells can expand hematopoietic and neuroglial progenitors in vitro. , 2004, Experimental cell research.

[26]  K. Shyu,et al.  Combined cord blood stem cells and gene therapy enhances angiogenesis and improves cardiac performance in mouse after acute myocardial infarction , 2005, European journal of clinical investigation.

[27]  K. Kang,et al.  Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure. , 2007, Biochemical and biophysical research communications.

[28]  S. Rutella,et al.  Human cord blood CD133+ cells immunoselected by a clinical‐grade apparatus differentiate in vitro into endothelial‐ and cardiomyocyte‐like cells , 2007, Transfusion.

[29]  Y. Ha,et al.  Functional recovery after human umbilical cord blood cells transplantation with brain-derived neutrophic factor into the spinal cord injured rat , 2005, Acta Neurochirurgica.

[30]  Ching‐Jen Wang,et al.  Shockwave Stimulates Oxygen Radical‐Mediated Osteogenesis of the Mesenchymal Cells From Human Umbilical Cord Blood , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[31]  S. U. Kim,et al.  Retinoic acid‐mediated induction of neurons and glial cells from human umbilical cord‐derived hematopoietic stem cells , 2004, Journal of neuroscience research.

[32]  M. Pesce,et al.  Differentiation of Human Umbilical Cord Blood – Derived Stem Cells in Ischemic Limb Tissues , 2003 .

[33]  M. Chopp,et al.  Intravenous Administration of Human Umbilical Cord Blood Reduces Neurological Deficit in the Rat after Traumatic Brain Injury , 2002, Cell transplantation.

[34]  Seung‐Woo Cho,et al.  Enhancement of angiogenic efficacy of human cord blood cell transplantation. , 2006, Tissue engineering.

[35]  Markus G. Manz,et al.  Development of a Human Adaptive Immune System in Cord Blood Cell-Transplanted Mice , 2004, Science.

[36]  R. Henning,et al.  Human Umbilical Cord Blood Mononuclear Cells in the Treatment of Acute Myocardial Infarction , 2011 .

[37]  T. Murohara,et al.  Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. , 2000, The Journal of clinical investigation.

[38]  Joshua M Hare,et al.  Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[39]  P. Wernet,et al.  A New Human Somatic Stem Cell from Placental Cord Blood with Intrinsic Pluripotent Differentiation Potential , 2004, The Journal of experimental medicine.

[40]  P. Sanberg,et al.  Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation. , 2003, Journal of hematotherapy & stem cell research.

[41]  Hoon Han,et al.  A 37-year-old spinal cord-injured female patient, transplanted of multipotent stem cells from human UC blood, with improved sensory perception and mobility, both functionally and morphologically: a case study. , 2005, Cytotherapy.

[42]  L. Yao,et al.  Derivation of Endothelial Cells from CD34− Umbilical Cord Blood , 2004, Stem cells.

[43]  S. Kakinuma,et al.  Human Umbilical Cord Blood as a Source of Transplantable Hepatic Progenitor Cells , 2003, Stem Cells.

[44]  W. Low,et al.  Transplantation of a novel cell line population of umbilical cord blood stem cells ameliorates neurological deficits associated with ischemic brain injury. , 2005, Stem cells and development.

[45]  P. Sanberg,et al.  Intravenous versus intrastriatal cord blood administration in a rodent model of stroke , 2003, Journal of neuroscience research.

[46]  Santhosh K. P. Kumar,et al.  Soluble EphB4 regulates choroidal endothelial cell function and inhibits laser-induced choroidal neovascularization. , 2005, Investigative ophthalmology & visual science.

[47]  L. Denner,et al.  Production of stem cells with embryonic characteristics from human umbilical cord blood , 2005, Cell proliferation.

[48]  P. Sanberg,et al.  Timing of Cord Blood Treatment after Experimental Stroke Determines Therapeutic Efficacy , 2006, Cell transplantation.

[49]  P. Walczak,et al.  Human Umbilical Cord Blood Progenitors: The Potential of These Hematopoietic Cells to Become Neural , 2005, Stem cells.

[50]  S. Hoerstrup,et al.  Engineering of biologically active living heart valve leaflets using human umbilical cord-derived progenitor cells. , 2006, Tissue engineering.

[51]  D. Spitkovsky,et al.  Cell Transplantation Improves Ventricular Function After a Myocardial Infarction: A Preclinical Study of Human Unrestricted Somatic Stem Cells in a Porcine Model , 2005, Circulation.

[52]  P. Sanberg,et al.  Central Nervous System Entry of Peripherally Injected Umbilical Cord Blood Cells Is Not Required for Neuroprotection in Stroke , 2004, Stroke.

[53]  A. Dejana,et al.  Cord blood (CB) stem cells for wound repair. Preliminary report of 2 cases. , 2004, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[54]  W. Ansorge,et al.  Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. , 2005, Experimental hematology.

[55]  R. Guignard,et al.  Reconstructed Human Cornea Produced in vitro by Tissue Engineering , 1999, Pathobiology.

[56]  Dolores Baksh,et al.  Human Umbilical Cord Perivascular (HUCPV) Cells: A Source of Mesenchymal Progenitors , 2005, Stem cells.

[57]  A. Reddi,et al.  Transplantation of human umbilical cord blood cells improves glycemia and glomerular hypertrophy in type 2 diabetic mice. , 2004, Biochemical and biophysical research communications.

[58]  Y. Suematsu,et al.  Human umbilical cord blood cells improve cardiac function after myocardial infarction. , 2005, Biochemical and biophysical research communications.

[59]  M. Chopp,et al.  Intravenous Administration of Human Umbilical Cord Blood Reduces Behavioral Deficits After Stroke in Rats , 2001, Stroke.

[60]  N. Ende,et al.  NOD/LtJ type I diabetes in mice and the effect of stem cells (Berashis) derived from human umbilical cord blood. , 2002, Journal of medicine.

[61]  P. Sanberg,et al.  Infusion of Human Umbilical Cord Blood Cells in a Rat Model of Stroke Dose-Dependently Rescues Behavioral Deficits and Reduces Infarct Volume , 2004, Stroke.

[62]  J. González-Porras,et al.  Peripheral endothelial progenitor cells (CD133 +) for therapeutic vasculogenesis in a patient with critical limb ischemia. One year follow-up. , 2007, Cytotherapy.

[63]  Raphael Guzman,et al.  Cell Transplantation Therapy for Stroke , 2007, Stroke.

[64]  J. Leor,et al.  Human Umbilical Cord Blood–Derived CD133+ Cells Enhance Function and Repair of the Infarcted Myocardium , 2006, Stem cells.

[65]  Koichi Matsumoto,et al.  Development of angiogenic cell and gene therapy by transplantation of umbilical cord blood with vascular endothelial growth factor gene. , 2004, Hypertension research : official journal of the Japanese Society of Hypertension.

[66]  P. Sanberg,et al.  Cytokines produced by cultured human umbilical cord blood (HUCB) cells: Implications for brain repair , 2006, Experimental Neurology.

[67]  P. Fu,et al.  Direct comparison of umbilical cord blood versus bone marrow-derived endothelial precursor cells in mediating neovascularization in response to vascular ischemia. , 2006, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[68]  Hamdi M. Abu-Ali,et al.  Human Umbilical Cord Blood Mononuclear Cells for the Treatment of Acute Myocardial Infarction , 2004, Cell transplantation.

[69]  L. Lagneaux,et al.  Mesenchymal Stem Cells Derived from CD133‐Positive Cells in Mobilized Peripheral Blood and Cord Blood: Proliferation, Oct4 Expression, and Plasticity , 2005, Stem cells.

[70]  Marcin Jurga,et al.  Neural stem-like cell line derived from a nonhematopoietic population of human umbilical cord blood. , 2006, Stem cells and development.