iCell Cardiomyocytes

Published Research


iCell Cardiomyocytes

Reference

Notes

Sirenko O, Cromwell EF, et al.
(2013 Dec 15)

Toxicol Appl Pharmacol.
273(3):500-07.

Assessment of Beating Parameters in Human Induced Pluripotent Stem Cells Enables Quantitative In Vitro Screening for Cardiotoxicity.

Exposure of iCell Cardiomyocytes to 131 compounds and multiple physiological endpoints to develop a phenotypic and predictive model for assessing cardiotoxicity in a 384-well format.

Uesugi M, Ojima A, et al.
(2013 Dec 1)

J Pharmacol Toxicol Methods.
[Epub ahead of print]

Low-density Plating Is Sufficient to Induce Cardiac Hypertrophy and Electrical Remodeling in Highly Purified iPS Cell-derived Cardiomyocytes.

Demonstration that iCell Cardiomyocytes can be induced to show relevant and appropriate pathological responses and provide utility as an in vitro model for understanding and treating cardiac disease. Cardiac hypertrophy was induced in iCell Cardiomyocytes through low-density plating. The hypertrophic condition resulted in larger cardiomyocytes and altered gene and protein expression profiles.

Carlson C, Koonce C, et al.
(2013 Dec 1)

J Biomol Screen.
18(10):1203-11.

Phenotypic Screening with Human iPS Cell-derived Cardiomyocytes: HTS-compatible Assays for Interrogating Cardiac Hypertrophy.

Development of high throughput protein-based assays using iCell Cardiomyocytes as a system to induce and ameliorate hypertrophy.

Guo L, Coyle I, et al.
(2013 Dec)

Toxicol Sci.
136(2):581-94.

Refining the Human iPSC-cardiomyocyte Arrhythmic Risk Assessment.

Demonstration that iCell Cardiomyocytes were able to predict QT prolongation and arrhythmia with greater accuracy than current in vitro models when challenged with a set of 118 public and proprietary compounds.

Doherty K, Wappel R, et al.
(2013 Oct 1)

Toxicol Appl Pharmacol.
272(1):245-55.

Multi-parameter In Vitro Toxicity Testing of Crizotinib, Sunitinib, Erlotinib, and Nilotinib in Human Cardiomyocytes.

Use of iCell Cardiomyocytes and multiparametric analysis to predict the cardiotoxic profile of four FDA-approved tyrosine kinase inhibitors (TKi) molecules that showed unexpected toxicity in humans.

Fine M, Lu F-M, et al.
(2013 Jun 26)

Am J Physiol Cell Physiol.
[Epub ahead of print]

Human-induced Pluripotent Stem Cell-derived Cardiomyocytes for Studies of Cardiac Ion Transporters.

Demonstration that cardiac ion transporters in iCell Cardiomyocytes are similar in expression levels and activity to adult non-rodent cardiomyocytes. Various cellular techniques, including Halo® fusion proteins, were used to show native ion transporter function and modulation through small molecules and regulatory proteins in iCell Cardiomyocytes.

Harris K, Aylott Y, et al.
(2013 Aug)

Toxicol Sci.
134(2):412-26.

Comparison of Electrophysiological Data from Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (hiPSC-CMs) to Functional Preclinical Safety Assays.

Shows the pharmacology of ion channel blockade in comparison to existing functional cardiac electrophysiology studies. The MEA data shows that hiPSC-CMs demonstrate relevant pharmacology and show excellent correlations to existing functional cardiac electrophysiological assays.

Rao C, Prodromakis T, et al.
(2013 Mar)

Biomaterials.
34(10):2399-411.

The Effect of Microgrooved Culture Substrates on Calcium Cycling of Cardiac Myocytes Derived from Human Induced Pluripotent Stem Cells.

Demonstrates how combining advanced cell culture techniques with advanced cellular biology can create a more robust recapitulation of native cellular behavior. Cellular alignment, sarcomeric organization, and Ca2+ cycling properties were altered when iCell Cardiomyocytes were cultured on a structured substrate.

Schweikart K, Guo L, et al.
(2012 Dec 20)

Toxicol In Vitro.
27:745-51.

The Effects of Jaspamide on Human Cardiomyocyte Function and Cardiac Ion Channel Activity.

Use of iCell Cardiomyocytes to demonstrate that the acute in vivo toxicity of jaspamide, an anti-neoplastic agent, were due to toxic effects on cardiomyocytes.

Jehle J, Ficker E, et al.
(2012 Oct 12)

British J Pharm
[Epub ahead of print]

Mechanisms of Zolpidem-induced Long QT Ayndrome: Acute Inhibition of Recombinant hERG K+ Channels and Action Potential Prolongation in Human Cardiomyocytes Derived from Induced Pluripotent Stem Cells.

Demonstration of cardiac action potential duration prolongation in iCell Cardiomyocytes by zolpidem, a short-acting hypnotic drug prescribed to treat insomnia that has been clinically associated with acquired long QT syndrome (LQTS) and torsade de pointes (TdP).

Puppala D, Collis LP, et al.
(2012 Sep 14)

Toxicol Sci
131(1):292-301.

Comparative Gene Expression Profiling in Human Induced Pluripotent Stem Cell Derived Cardiocytes and Human and Cynomolgus Heart Tissue.

Comparison of the gene expression profile of iCell Cardiomyocytes post-thaw over a period of 42 days in culture to human fetal and adult profiles as well as adult cynomolgus nonhuman primate. Evaluation of iCell Cardiomyocytes contractility demonstrated functional and pharmacological correlations with myocytes isolated from adult NHP hearts.

Sirenko O, Crittenden C, et al.
(2012 Sep 12)

J Biomol Screen.
18(1): 39-53.

Multiparameter In Vitro Assessment of Compound Effects on Cardiomyocyte Physiology Using iPSC Cells.

Assessment of cellular physiology and small molecule effects using iCell Cardiomyocytes in conjunction with the FLIPR platform as a high throughput methodology.

Cerignoli R, Charlot D, et al.
(2012 Aug 25)

J Pharmacol Toxicol Methods
66(3):246-56.

High Throughput Measurement of Ca2+ Dynamics for Drug Risk Assessment in Human Stem Cell-derived Cardiomyocytes by Kinetic Image Cytometry.

Use of a novel kinetic imaging cytometry (KIC) for automated cell-by-cell analyses of iCell Cardiomyocytes via intracellular fluorescence Ca2+ indicators. Intracellular calcium concentration ([Ca2+]i) was measured at 30 ms resolution from hundreds of individual cells/well of 96-well plates in seconds to provide kinetic details on the effects of known cardiotoxic and arrhythmogenic drugs.

Mioulane M, Foldes G, et al.
(2012 Aug 16)

J of Cardiovasc Trans Res
5:593-604.

Development of High Content Imaging Methods for Cell Death Detection in Human Pluripotent Stem Cell-derived Cardiomyocytes.

Use of iCell Cardiomyocytes and other cardiac tissue cells to develop a novel simple and scalable humanized fluorescent assay system to detect nuclear remodeling, mitochondrial status, apoptosis, and necrosis on an automated microscopy platform.

Rana P, Anson BD, et al.
(2012 Jul 27)

Toxicol Sci
130:117-31.

Characterization of Human-induced Pluripotent Stem Cell-derived Cardiomyocytes: Bioenergetics and Utilization in Safety Screening.

Investigation of the bioenergetics of iCell Cardiomyocytes using a variety of energy substrates. When fatty acids are available, iCell Cardiomyocytes utilize fatty acid oxidation to generate ATP. iCell Cardiomyocytes also showed expected responses to mitochondrial toxicants.

Reynolds JG, Geretti E, et al.
(2012 Jul 1)

Toxicol Appl Pharmacol
262:1-10.

HER2-targeted Liposomal Doxorubicin Displays Enhanced Anti-tumorigenic Effects without Associated Cardiotoxicity.

Use of iCell Cardiomyocytes and native cardiomyocytes demonstrate the lack of cardiotoxicity associated with HER-2 targeted liposomal doxorubicin. Data were used in submission of an Investigational New Drug (IND) application.

Zhi D, Irvin MR, et al.
(2012 May 28)

Front Genet
3:92.

Whole-exome Sequencing and an iPSC-derived Cardiomyocyte Model Provides a Powerful Platform for Gene Discovery in Left Ventricular Hypertrophy.

Identification of novel polymorphisms associated with LVH from clinical populations and generation of a novel cellular model of LVH using iCell Cardiomyocytes.

Lee P, Kloss M, et al.
(2012 May 8)

Circ Res
110(12):1556-63.

Simultaneous Voltage and Calcium Mapping of Genetically Purified Human Induced Pluripotent Stem Cell-derived Cardiac Myocyte Monolayers. Circ Res. Published online ahead of print.

Development of a multiparametric imaging system using iCell Cardiomyocytes to simultaneously measure action potential and intracellular calcium wave propagation. The described system can be utilized for the study of arrhythmia mechanisms and offers advantages over commonly used rodent models.

Babiarz JE, Ravon M, et al.
(2012 Jan 4)

Stem Cells
21(11):1956-65.

Determination of the Human Cardiomyocyte mRNA and miRNA Differentiation Network by Fine-scale Profiling.

Detailed comparison of the mRNA and miRNA transcriptomes across differentiating iCell Cardiomyocytes and biopsies from fetal, adult, and hypertensive human hearts.

Jonsson MKB, Wang QD, et al.
(2011 Nov 15)

Assay and Drug Dev Tech
9 (6):1-11.

Impedance-based Detection of Beating Rhythm and Proarrhythmic Effects of Compounds on Stem Cell-derived Cardiomyocytes.

Demonstration of the utility of impedance-based measurements to detect compound effects on beating frequency and arrhythmias using iCell Cardiomyocytes with the xCELLigence RTCA Cardio System (Roche Applied Science). Using this system, the beating frequency of iCell Cardiomyocyte monolayers was stably recorded over several days, and the system detected changes in beating frequency and amplitude in response to reference compounds.

Ma J, Guo L, et al.
(2011 Sep 2)

Am J Physiol Heart Circ Physiol
301:H2006-H2017.

High Purity Human-induced Pluripotent Stem Cell-derived Cardiomyocytes: Electrophysiological Properties of Action Potentials and Ionic Currents.

Characterization study demonstrating that iCell Cardiomyocytes display cellular electrophysiological properties similar to human cardiomyocytes.

Cohen JD, Babiarz JE, et al.
(2011 Aug 27)

Toxicol Appl Pharmacol
257:74-83.

Use of Human Stem Cell Derived Cardiomyocytes to Examine Sunitinib Mediated Cardiotoxicity and Electrophysiological Alterations.

Elucidation of the molecular mechanisms of sunitinub-induced cardiotoxicity. A role for AMP-activated protein kinase (AMPK) and ribosomal 6 kinase (RSK) was hypothesized based on rodent models. However, data generated using human iCell Cardiomyocytes indicate that AMPK and RSK are not major components of sunitinib-induced cardiotoxicity, which is likely due to the simultaneous inhibition of multiple kinases.

Guo L, Abrams RM, et al.
(2011 Jun 20)

Toxicol Sci
123(1):281-289.

Estimating the Risk of Drug-induced Proarrhythmia Using Human Induced Pluripotent Stem Cell-derived Cardiomyocytes.

Analysis of 28 compounds with known cardiac effects was performed using iCell Cardiomyocytes and the xCELLigence RTCA Cardio System (Roche Applied Science). Compound-specific changes in beat rate and/or the amplitude of the impedance measurement were detected in concordance with clinical findings. These results were confirmed using iCell Cardiomyocytes and the multielectrode array (MEA) platform.

Guo L, Qian JY, et al.
(2011 Jun 15)

Cell Physiol Biochem
27 (5):453-462.

The Electrophysiological Effects of Cardiac Glycosides in Human iPSC-derived Cardiomyocytes and in Guinea Pig Isolated Hearts.

Pharmacological and toxicological effects of cardiac glycosides (ouabain, digoxin) and the L-type Ca2+ channel antagonist nifedipine on iCell Cardiomyocytes were measured by multielectrode array (MEA). The observed changes in field potential duration and Ca2+ wave amplitude correlated with the compounds’ effects on QT interval and contractility in guinea pig Langendorff hearts. These data demonstrate that iCell Cardiomyocytes area suitable in vitro model for cardioactive ion channel and transporter modulators.


iCell Neurons

Reference

Notes

Whitemarsh RC, Tepp WH, et al.
(2013 Oct 8)

Infect Immun.
81:3894-3902.

Characterization of Botulinum Neurotoxin A Subtypes 1 through 5 by Investigation of Activities in Mice, in Neuronal Cell Cultures, and In Vitro.

Use of iCell Neurons, along with other commonly used in vitro and in vivo models, to characterize the various subtypes of BoNT/A. The results showed distinct in vitro and in vivo toxicological properties between the mouse bioassay (MBA) and in vitro human cell models, thus questioning the predictivity of the MBA.

Grose C, Xiaoli Y, et al.
(2013 Sep)

J Virol.
87(17):9643-8

Aberrant Virion Assembly and Limited gC Production in Varicella Zoster Virus Infected Neurons.

Use of the iCell Neuron in vitro model of varicella zoster virus (VZV) infection developed by Yu, et al. (2013) to determine whether diminished production of virion components and/or final assembly of complete virions play a role in limiting productive virus infection.

Xu X, Lei Y, et al.
(2013 Mar)

Stem Cell Res.
10(2):213-227
.

Prevention of β-Amyloid Induced Toxicity in Human iPS Cell-derived Neurons by Inhibition of Cyclin-dependent Kinases and Associated Cell Cycle Events.

Demonstration of the first known use of human iPS cell-derived neurons (iCell Neurons) to model Alzheimer’s disease through Aß toxicity, showing potential for use in high throughput drug screening. Several hundred compounds from a GSK proprietary compound library were screened. Nineteen compounds were selected as hits based on the selection criteria; one of them was a Cdk2 inhibitor, confirming the reliability and sensitivity of GSK’s screening platform based on human iPS cell-derived neurons.

Gill J, Chatzidaki A, et al.
(2013 Jan 29)

PLoS ONE.
8:e55047.

Contrasting Properties of α7-Selective Orthosteric and Allosteric Agonists Examined on Native Nicotinic Acetylcholine Receptors.

Use of iCell Neurons to evaluate the potential use of three pharmacologically distinct α7-selective nicotinic ligands (an orthosteric agonist, a positive allosteric modulator, and a nondesensitizing allosteric agonist) for the characterization of native nAChRs.

Yu X, Seitz S, et al.
(2013 Feb)

J Neurovirol.
19(1):75-81.

Varicella Zoster Virus Infection of Hghly Pure Terminally Differentiated Human Neurons.

Development of an in vitro model of varicella zoster virus (VZV) infection using highly pure iCell Neurons. Infection of iCell Neurons with VZV produces a nonproductive infection in the absence of apoptosis, thus enabling molecular analysis of VZV-neuronal relationship and studies of the mechanisms of VZV reactivation.

Haythornthwaite A, Stoelzle A, et al.
(2012 Aug 24)

J Biomol Screen.
17(9):1264-1272

Characterizing Human Ion Channels in Induced Pluripotent Stem Cell-derived Neurons.

Characterization study demonstrating that iCell Neurons display cellular electrophysiological properties similar to human neurons using manual and automated patch clamp recordings.

Chai X, Dage JL, et al.
(2012 Jun 2)

Neurobiol Dis.
48(3):356-366

Constitutive Secretion of Tau Protein by an Unconventional Mechanism.

Demonstration that iCell Neurons release a small percentage of intracellular tau by a nonconventional secretion pathway at comparable levels occurring under physiological conditions in vivo. To study this mechanism, a system is needed to eliminate confounding cell death and have enough signal to detect very small amounts of tau secreted. iCell Neurons enable the study of this mechanism, overcoming the limitations of assay sensitivity seen in primary neurons in intact animals.

Whitemarsh RC, Strathman MJ, et al.
(2012 Jan 5)

Toxicol Sci.
126(2):426-35.

Novel Application of Human Neurons Derived from Induced Pluripotent Stem Cells for Highly Sensitive Botulinum Neurotoxin Detection.

Evaluation of iCell Neurons as a novel, species relevant model system for Clostridium botulinum neurotoxin (BoNT) detection and mechanistic studies. Compared with primary rat spinal cord cells, iCell Neurons showed equal or increased sensitivity, a steeper dose-response curve and a more complete SNARE protein target cleavage. These data suggest that iCell Neurons provide an ideal and highly sensitive platform for BoNT potency determination neutralizing antibody detection and for mechanistic studies.


iCell Hepatocytes

Reference

Notes

Sirenko O, Hesley J, et al.
(2013 Nov 14)

Assay Drug Dev Technol.
[Epub ahead of print]

High-content Assays for Hepatotoxicity Using Induced Pluripotent Stem Cell-derived Cells.

Use of iCell Hepatocytes in the screening of a panel of 208 known hepatotoxic and 30 safe compounds by high content analysis for multiple toxic endpoint readouts.


MyCell Products

Reference

Notes

Phillips MJ, Wallace
KA, et al
(2012 Apr)

Invest Ophthalmol Vis Sci
53(4):2007-2019

Blood-derived Human iPS Cells Generate Optic Vesicle-like Structures with the Capacity to Form Retinal Laminae and Develop Synapses

Use of human blood-derived iPS cells to generate optical vesicle-like structures that have the capacity to self-assembly into rudimentary neuroretinal structures that express markers indicative of chemical and electrical synapses. This study demonstrates the creation of a novel and highly convenient donor cell source for iPS cell-based retinal studies.


Cellular Dynamics Research & Development

Reference

Notes

Mack AA, Kroboth S, et al
(2011 Nov 22)

PLoS ONE
6(11):e27956

Generation of Induced Pluripotent Stem Cells from CD34+ Cells across Blood Drawn from Multiple Donors with Non-integrating Episomal Vectors

Demonstration of reprogramming from a single vial of blood or less using cells expressing the early lineage marker CD34 as well as from unpurified peripheral blood mononuclear cells.

Ma J, Guo L, et al
(2011 Sep 2)

Am J Physiol Heart Circ Physiol
301(5):H2006-17

High Purity Human-induced Pluripotent Stem Cell-derived Cardiomyocytes: Electrophysiological Properties of Action Potentials and Ionic Currents

Performance of detailed electrophysiological characterization of highly pure hiPSC-derived cardiomyocytes. Action potentials (APs) were recorded from spontaneously beating cardiomyocytes using a perforated patch method and had atrial-, nodal-, and ventricular-like properties.

Rajesh D, Dickerson S, et al
(2011 Jun 27)

Blood
118(7):1797-1800

Human Lymphoblastoid B Cell Lines Reprogrammed to EBV-free Induced Pluripotent Stem Cells

Generation of iPSCs from two LCLs via a feeder-free episomal method using a cocktail of transcription factors and small molecules. LCL-derived iPSCs exhibited normal karyotype, expressed pluripotency markers, lost oriP/EBNA-1 episomal vectors, generated teratomas, retained donor identity and differentiatedin vitro into hematopoietic, cardiac, neural, and hepatocyte-like lineages.

Anson BD, Kolaja KL, and Kamp TJ
(2011 Jan)

Clin Pharmacol Ther
89(5):754-758

Opportunities for Use of Human iPS Cells in Predictive Toxicology

Description of the properties of human induced pluripotent stem (iPS) cells that make them a promising source for toxicity assessment, highlight the progress to date, and point out the important roadblocks that remain.


Stem Cell Technology

iPS Cells

References

Notes

Phillips MJ, Wallace
KA, et al
(2012 Apr)

Ophthalmol Vis Sci
53(4):2007-2019

Blood-derived Human iPS Cells Generate Optic Vesicle-like Structures with the Capacity to Form Retinal Laminae and Develop Synapses

Demonstration that human blood-derived iPSCs can generate retinal cell types and that cultured TiPSC-OVs have the capacity to self-assemble into rudimentary neuroretinal structures and express markers indicative of chemical and electrical synapses.

Meyer JS, Howden
SE, et al
(2011 Aug)

Stem Cells
29:1206–1218

Optic Vesicle Structures Derived from Human Pluripotent Stem Cells Facilitate a Customized Approach to Retinal Disease Treatment

Demonstration that three-dimensional populations of retinal progenitor cells (RPCs) can be isolated from early forebrain populations in both human embryonic stem cell and hiPSC cultures, providing a valuable tool for developmental, functional, and translational studies. Using the established protocol, a transient population of optic vesicle (OV)-like structures that arose during a time period appropriate for normal human retinogenesis were identified.

Chen G, Gulbranson
DR, et al
(2011 Apr 10)

Nat Methods
8(5):424–429

Chemically Defined Conditions for Human iPS Cell Derivation and Culture

Use of new medium (E8) and vitronectin-coated surfaces to demonstrate improved derivation efficiencies of vector-free human iPS cells with an episomal approach.

Howden SE, Gore A, et al
(2011 Apr 4)

Proc Natl Acad Sci USA
108(16):6537-6542

Genetic Correction and Analysis of Induced Pluripotent Stem Cells from a Patient with Gyrate Atrophy

Isolation of iPS cells free of transgene sequences from a patient with gyrate atrophy caused by a point mutation in the gene encoding ornithine-δ-aminotransferase (OAT) and use of homologous recombination to correct the genetic defect.

Yu J, Chau FK, et al
(2011 Mar 1)

PLoS ONE
6(3):e17557

Efficient Feeder-Free Episomal Reprogramming with Small Molecules

Establishment of a feeder-free reprogramming condition using chemically defined medium with bFGF and N2B27 supplements and chemically defined human ESC medium mTeSR1 for the derivation of footprint-free human iPSCs.

Hu K, Yu J, et al
(2011 Feb 4)

Blood
117:14e109-e119

Efficient Generation of Transgene-free Induced Pluripotent Stem Cells from Normal and Neoplastic Bone Marrow and Cord Blood Mononuclear Cells

Demonstrated that iPSCs free of transgene and vector sequences could be efficiently generated from human bone marrow (BM) and cord blood (CB) mononuclear cells using non-integrating episomal vectors.

Brown ME, Rondon E, et al
(2010 Jun 29)

PLoS ONE
5(6): e11373

Derivation of Induced Pluripotent Stem Cells from Human Peripheral Blood T Lymphocytes

Generation of T lymphocyte-derived iPSCs from small, clinically advantageous volumes of non-mobilized peripheral blood. These T-cell derived iPSCs retain a normal karyotype and genetic identity to the donor.

Yu J and Thomson JA
(2009)

Essentials of Stem Cell Biology, 2nd edition, Elsevier Academic Press

Induced Pluripotent Stem Cell Derivation

Description of basic biology/mechanisms, early development, ectoderm, mesoderm, endoderm, methods to application of stem cells to specific human diseases, regulation and ethics, and patient perspectives, and more in the field of stem cells.

Yu J, Hu K, et al
(2009 Mar 26)

Science
324(5928):797-801

Human Induced Pluripotent Stem Cells Free of Vector and Transgene Sequences

Derivation of human iPS cells with the use of nonintegrating episomal vectors.

Ebert AD, Yu J, et al
(2008 Dec 21)

Nature
457(7227):277-80

Induced Pluripotent Stem Cells from a Spinal Muscular Atrophy Patient

Generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy.

Yu J and Thomson JA
(2008 Aug 1)

Genes Dev
22(15):1987-97

Pluripotent Stem Cell Lines

Review of the family of pluripotent cell lines derived from early embryos and from germ cells, comparing them with more recently described induced pluripotent stem cells.

Yu J, Vodyanik MA, et al
(2007 Nov 20)

Science
318(5858):1917-20

Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells

Showing that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem cells.

Yu J, Vodyanik MA, et al
(2005 Oct 6)

Stem Cells
24(1):168-76

Human Embryonic Stem Cells Reprogram Myeloid Precursors Following Cell-Cell Fusion

Reprogramming of the nuclei of hESC-derived myeloid precursors following cell-cell fusion.

Hematopoietic Cells

Dias J, Gumenyuk M, et al
(2011 May 11)

Stem Cells Dev
20(9):1639-47

Generation of Red Blood Cells from Human Induced Pluripotent Stem Cells

Description of an approach for the efficient generation of RBCs from hiPSC/hESCs using an OP9 co-culture system to induce hematopoietic differentiation followed by selective expansion of erythroid cells in serum-free media with erythropoiesis-supporting cytokines.

Slukvin II and Vodyanik M
(2011 May 1)

Cell Cycle
10(9):1370-3

Endothelial Origin of Mesenchymal Stem Cells

Demonstrating that mesodermal MSCs arise from APLNR+ precursors with angiogenic potential, mesenchymoangioblasts.