The Therapeutic Potential of Stem Cells for Bronchopulmonary Dysplasia: “It’s About Time” or “Not so Fast” ?

Objective: While the survival of extremely premature infants has improved over the past decades, the rate of complications – especially for bronchopulmonary dysplasia (BPD) – remains un-acceptably high. Over the past 50 years, no safe therapy has had a substantial impact on the incidence and severity of BPD. Methods: This may stem from the multifactorial disease pathogenesis and the increasing lung imma-turity. Mesenchymal Stromal Cells (MSCs) display pleiotropic effects and show promising results in neonatal rodents in preventing or rescuing lung injury without adverse effects. Early phase clinical trials are now underway to determine the safety and efficacy of this therapy in extremely premature infants. Results and Conclusion: This review summarizes our current knowledge about MSCs, their mecha-nism of action and the results of preclinical studies that provide the rationale for early phase clinical trials and discuss remaining gaps in our knowledge

[1]  Siddaraju Boregowda,et al.  Mesenchymal Stem Cells: The Moniker Fits the Science , 2018, Stem cells.

[2]  B. Thébaud,et al.  Bronchopulmonary Dysplasia: Where Have All the Stem Cells Gone?: Origin and (Potential) Function of Resident Lung Stem Cells , 2017, Chest.

[3]  B. Thébaud,et al.  Human Umbilical Cord Mesenchymal Stromal Cells Improve Survival and Bacterial Clearance in Neonatal Sepsis in Rats. , 2017, Stem cells and development.

[4]  J. Hare,et al.  Stromal derived factor-1 mediates the lung regenerative effects of mesenchymal stem cells in a rodent model of bronchopulmonary dysplasia , 2017, Respiratory Research.

[5]  M. Inan,et al.  Mesenchymal stem cells increase antioxidant capacity in intestinal ischemia/reperfusion damage. , 2017, Journal of pediatric surgery.

[6]  Jeong Hun Shin,et al.  Bone marrow mesenchymal stem cell-derived vascular endothelial growth factor attenuates cardiac apoptosis via regulation of cardiac miRNA-23a and miRNA-92a in a rat model of myocardial infarction , 2017, PloS one.

[7]  Ji Hye Kim,et al.  Two‐Year Follow‐Up Outcomes of Premature Infants Enrolled in the Phase I Trial of Mesenchymal Stem Cells Transplantation for Bronchopulmonary Dysplasia , 2017, The Journal of pediatrics.

[8]  A. Caplan.  Mesenchymal Stem Cells: Time to Change the Name! , 2017, Stem cells translational medicine.

[9]  C. Nardiello,et al.  Looking ahead: where to next for animal models of bronchopulmonary dysplasia? , 2016, Cell and Tissue Research.

[10]  Siddaraju Boregowda,et al.  Quantifiable Metrics for Predicting MSC Therapeutic Efficacy , 2016, Journal of stem cell research & therapy.

[11]  S. Somashekar,et al.  The Effect of Gender on Mesenchymal Stem Cell (MSC) Efficacy in Neonatal Hyperoxia-Induced Lung Injury , 2016, PloS one.

[12]  Zhaohua Zhang,et al.  Protective effects of BMSCs in combination with erythropoietin in bronchopulmonary dysplasia-induced lung injury. , 2016, Molecular medicine reports.

[13]  L. Yin,et al.  MicroRNA‐146b, a Sensitive Indicator of Mesenchymal Stem Cell Repair of Acute Renal Injury , 2016, Stem cells translational medicine.

[14]  A. Kirk,et al.  Cryopreserved Mesenchymal Stromal Cells Are Susceptible to T‐Cell Mediated Apoptosis Which Is Partly Rescued by IFNγ Licensing , 2016, Stem cells.

[15]  Hye Soo Yoo,et al.  Intratracheal transplantation of mesenchymal stem cells simultaneously attenuates both lung and brain injuries in hyperoxic newborn rats , 2016, Pediatric Research.

[16]  D. Prockop.  Inflammation, fibrosis, and modulation of the process by mesenchymal stem/stromal cells. , 2016, Matrix biology : journal of the International Society for Matrix Biology.

[17]  C. Bony,et al.  Antifibrotic, Antioxidant, and Immunomodulatory Effects of Mesenchymal Stem Cells in HOCl‐Induced Systemic Sclerosis , 2016, Arthritis & rheumatology.

[18]  A. Atıcı,et al.  Mesenchymal stem cell treatment in hyperoxia‐induced lung injury in newborn rats , 2016, Pediatrics international : official journal of the Japan Pediatric Society.

[19]  H. Chou,et al.  Human mesenchymal stem cells attenuate experimental bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia. , 2016, American journal of translational research.

[20]  I. Martin,et al.  International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials. , 2016, Cytotherapy.

[21]  Sukhmani Kaur,et al.  Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment , 2016, Stem cells international.

[22]  K. Akram,et al.  Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches , 2016, International journal of molecular sciences.

[23]  L. Ortiz,et al.  A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells , 2015, EBioMedicine.

[24]  H. Lee,et al.  Mesenchymal stem/stromal cells precondition lung monocytes/macrophages to produce tolerance against allo- and autoimmunity in the eye , 2015, Proceedings of the National Academy of Sciences of the United States of America.

[25]  B. Poindexter,et al.  Comparisons and Limitations of Current Definitions of Bronchopulmonary Dysplasia for the Prematurity and Respiratory Outcomes Program. , 2015, Annals of the American Thoracic Society.

[26]  Frank Caminita,et al.  Lung volume recruitment in a preterm pig model of lung immaturity. , 2015, American journal of physiology. Lung cellular and molecular physiology.

[27]  Hye Soo Yoo,et al.  Optimal Route for Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation to Protect Against Neonatal Hyperoxic Lung Injury: Gene Expression Profiles and Histopathology , 2015, PloS one.

[28]  Hye Soo Yoo,et al.  Cell type-dependent variation in paracrine potency determines therapeutic efficacy against neonatal hyperoxic lung injury. , 2015, Cytotherapy.

[29]  B. Thébaud,et al.  Stem Cells and Their Mediators – Next Generation Therapy for Bronchopulmonary Dysplasia , 2015, Front. Med..

[30]  Xiaohua Liu,et al.  Conditioned medium from umbilical cord mesenchymal stem cells induces migration and angiogenesis , 2015, Molecular medicine reports.

[31]  W. Ding,et al.  Bone marrow-derived mesenchymal stem cells protect against lung injury in a mouse model of bronchopulmonary dysplasia. , 2015, Molecular medicine reports.

[32]  B. Branger,et al.  Survival and morbidity of preterm children born at 22 through 34 weeks' gestation in France in 2011: results of the EPIPAGE-2 cohort study. , 2015, JAMA pediatrics.

[33]  John M Centanni,et al.  A reproducible immunopotency assay to measure mesenchymal stromal cell-mediated T-cell suppression. , 2015, Cytotherapy.

[34]  U. Kiechl‐Kohlendorfer,et al.  Bronchopulmonary Dysplasia Is Associated with Delayed Structural Brain Maturation in Preterm Infants , 2015, Neonatology.

[35]  R. Buddington,et al.  A preterm pig model of lung immaturity and spontaneous infant respiratory distress syndrome. , 2015, American journal of physiology. Lung cellular and molecular physiology.

[36]  Andrew F. Hill,et al.  Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper , 2015, Journal of extracellular vesicles.

[37]  L. O’Driscoll,et al.  Biological properties of extracellular vesicles and their physiological functions , 2015, Journal of extracellular vesicles.

[38]  C. D'Angio,et al.  Animal models of bronchopulmonary dysplasia. The preterm and term rabbit models. , 2014, American journal of physiology. Lung cellular and molecular physiology.

[39]  Megan O'Reilly,et al.  Animal models of bronchopulmonary dysplasia. The term rat models. , 2014, American journal of physiology. Lung cellular and molecular physiology.

[40]  J. Padbury,et al.  Intranasal versus intraperitoneal delivery of human umbilical cord tissue-derived cultured mesenchymal stromal cells in a murine model of neonatal lung injury. , 2014, The American journal of pathology.

[41]  D. Prockop,et al.  TSG-6 as a biomarker to predict efficacy of human mesenchymal stem/progenitor cells (hMSCs) in modulating sterile inflammation in vivo , 2014, Proceedings of the National Academy of Sciences.

[42]  V. Bhandari,et al.  Animal models of bronchopulmonary dysplasia. The term mouse models. , 2014, American journal of physiology. Lung cellular and molecular physiology.

[43]  B. Yoder,et al.  Animal models of bronchopulmonary dysplasia. The preterm baboon models. , 2014, American journal of physiology. Lung cellular and molecular physiology.

[44]  Hye Soo Yoo,et al.  Critical role of vascular endothelial growth factor secreted by mesenchymal stem cells in hyperoxic lung injury. , 2014, American journal of respiratory cell and molecular biology.

[45]  Shuzhen Chen,et al.  Therapeutic effects of mesenchymal stem cell-derived microvesicles on pulmonary arterial hypertension in rats , 2014, Acta Pharmacologica Sinica.

[46]  M. Hershenson,et al.  Paracrine regulation of fetal lung morphogenesis using human placenta-derived mesenchymal stromal cells. , 2014, The Journal of surgical research.

[47]  W. Lam,et al.  Actin Cytoskeletal Disruption following Cryopreservation Alters the Biodistribution of Human Mesenchymal Stromal Cells In Vivo , 2014, Stem cell reports.

[48]  Hye Soo Yoo,et al.  Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. , 2014, The Journal of pediatrics.

[49]  M. Epple,et al.  MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease , 2014, Leukemia.

[50]  Wei Huang,et al.  Ischemic Preconditioning Potentiates the Protective Effect of Stem Cells through Secretion of Exosomes by Targeting Mecp2 via miR-22 , 2014, PloS one.

[51]  J. Martins,et al.  Human umbilical cord tissue-derived mesenchymal stromal cells attenuate remodeling after myocardial infarction by proangiogenic, antiapoptotic, and endogenous cell-activation mechanisms , 2014, Stem Cell Research & Therapy.

[52]  A. Cartón,et al.  Pulmonary hypertension in bronchopulmonary dysplasia: Clinical findings, cardiovascular anomalies and outcomes , 2014, Pediatric pulmonology.

[53]  M. Chopp,et al.  MiR‐133b Promotes Neural Plasticity and Functional Recovery After Treatment of Stroke with Multipotent Mesenchymal Stromal Cells in Rats Via Transfer of Exosome‐Enriched Extracellular Particles , 2013, Stem cells.

[54]  Y. Cui,et al.  Therapeutic effect of exogenous bone marrow‑derived mesenchymal stem cell transplantation on silicosis via paracrine mechanisms in rats. , 2013, Molecular medicine reports.

[55]  Wenyu Lai,et al.  Mesenchymal stem cells protect against neonatal rat hyperoxic lung injury , 2013, Expert opinion on biological therapy.

[56]  Jieli Chen,et al.  Neuroprotective Effect of Human Placenta-Derived Cell Treatment of Stroke in Rats , 2013, Cell transplantation.

[57]  Wendell A. Lim,et al.  Cell-Based Therapeutics: The Next Pillar of Medicine , 2013, Science Translational Medicine.

[58]  S. Ikehara,et al.  Bone-Marrow-Derived Mesenchymal Stem Cells for Organ Repair , 2013, Stem cells international.

[59]  Y. Chang,et al.  Long-Term (Postnatal Day 70) Outcome and Safety of Intratracheal Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Neonatal Hyperoxic Lung Injury , 2013, Yonsei medical journal.

[60]  Hye Soo Yoo,et al.  Timing of Umbilical Cord Blood Derived Mesenchymal Stem Cells Transplantation Determines Therapeutic Efficacy in the Neonatal Hyperoxic Lung Injury , 2013, PloS one.

[61]  D. Emery,et al.  Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia , 2012, Thorax.

[62]  Neil Marlow,et al.  Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies) , 2012, BMJ : British Medical Journal.

[63]  Sara Conti,et al.  Mesenchymal stem cell therapy promotes renal repair by limiting glomerular podocyte and progenitor cell dysfunction in adriamycin-induced nephropathy. , 2012, American journal of physiology. Renal physiology.

[64]  Wenyu Lai,et al.  Bone marrow mesenchymal stem cells attenuate lung inflammation of hyperoxic newborn rats , 2012, Pediatric transplantation.

[65]  Rochelle Cutrone,et al.  Development of a surrogate angiogenic potency assay for clinical-grade stem cell production. , 2012, Cytotherapy.

[66]  M. Fontaine,et al.  Harnessing the Immunomodulatory and Tissue Repair Properties of Mesenchymal Stem Cells to Restore β Cell Function , 2012, Current Diabetes Reports.

[67]  B. Thébaud,et al.  Lung injury in preterm neonates: the role and therapeutic potential of stem cells. , 2012, Antioxidants & redox signaling.

[68]  E. Gray,et al.  Human Mesenchymal Stem Cells Increase Anti-oxidant Defences in Cells Derived from Patients with Friedreich’s Ataxia , 2012, The Cerebellum.

[69]  Carla F. Kim,et al.  Bronchioalveolar stem cells increase after mesenchymal stromal cell treatment in a mouse model of bronchopulmonary dysplasia. , 2012, American journal of physiology. Lung cellular and molecular physiology.

[70]  B. Thébaud,et al.  Preconditioning enhances the paracrine effect of mesenchymal stem cells in preventing oxygen-induced neonatal lung injury in rats. , 2012, Stem cells and development.

[71]  G. Hansmann,et al.  Pulmonary Circulation | April-june 2012 | Vol 2 | No 2 170 Mesenchymal Stem Cell-mediated Reversal of Bronchopulmonary Dysplasia and Associated Pulmonary Hypertension , 2022 .

[72]  A Ohlsson,et al.  Outcomes of preterm infants <29 weeks gestation over 10-year period in Canada: a cause for concern? , 2012, Journal of Perinatology.

[73]  A. Angelini,et al.  Stem-cell therapy in an experimental model of pulmonary hypertension and right heart failure: role of paracrine and neurohormonal milieu in the remodeling process. , 2011, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[74]  S. Abman.  Pulmonary Vascular Disease and Bronchopulmonary Dysplasia: Evaluation and Treatment of Pulmonary Hypertension , 2011 .

[75]  C. Bancone,et al.  Epithelial-mesenchymal transition of epicardial mesothelium is a source of cardiac CD117-positive stem cells in adult human heart. , 2010, Journal of molecular and cellular cardiology.

[76]  P. Jarreau,et al.  [The use of postnatal corticosteroid therapy in premature infants to prevent or treat bronchopulmonary dysplasia: current situation and recommendations]. , 2010, Archives de pediatrie : organe officiel de la Societe francaise de pediatrie.

[77]  M. Matthay,et al.  Mesenchymal stem cells for acute lung injury: preclinical evidence. , 2010, Critical care medicine.

[78]  Y. Ni,et al.  In Vivo Differentiation of Magnetically Labeled Mesenchymal Stem Cells Into Hepatocytes for Cell Therapy to Repair Damaged Liver , 2010, Investigative radiology.

[79]  D. Prockop,et al.  Anti-inflammatory protein TSG-6 reduces inflammatory damage to the cornea following chemical and mechanical injury , 2010, Proceedings of the National Academy of Sciences.

[80]  B. Poindexter,et al.  Neonatal Outcomes of Extremely Preterm Infants From the NICHD Neonatal Research Network , 2010, Pediatrics.

[81]  S. Archer,et al.  Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in rats. , 2009, American journal of respiratory and critical care medicine.

[82]  O. Liang,et al.  Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease. , 2009, American journal of respiratory and critical care medicine.

[83]  G. Camussi,et al.  Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats , 2009, Journal of cellular and molecular medicine.

[84]  Alessandro Busca,et al.  Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. , 2009, Journal of the American Society of Nephrology : JASN.

[85]  Jae W. Lee,et al.  Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung , 2009, Proceedings of the National Academy of Sciences.

[86]  A. Loughran-Fowlds,et al.  THE NEWBORN LUNG: NEONATOLOGY QUESTIONS AND CONTROVERSIES , 2009 .

[87]  M. Rojas,et al.  Mesenchymal stem cells and inflammatory lung diseases. , 2009, Panminerva medica.

[88]  Li Chen,et al.  Mesenchymal stem cell therapy for diabetes through paracrine mechanisms. , 2008, Medical hypotheses.

[89]  H. Klingemann,et al.  Mesenchymal Stem Cells – Sources and Clinical Applications , 2008, Transfusion Medicine and Hemotherapy.

[90]  Pranela Rameshwar,et al.  Immunological properties of mesenchymal stem cells and clinical implications , 2008, Archivum Immunologiae et Therapiae Experimentalis.

[91]  X. Hong,et al.  [Intravenous infusion of rat bone marrow-derived mesenchymal stem cells ameliorates hyperoxia-induced lung injury in neonatal rats]. , 2007, Nan fang yi ke da xue xue bao = Journal of Southern Medical University.

[92]  E. Lam,et al.  Mesenchymal Stem Cells Inhibit Dendritic Cell Differentiation and Function by Preventing Entry Into the Cell Cycle , 2007, Transplantation.

[93]  M. Chopp,et al.  Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice , 2005, Experimental Neurology.

[94]  X. Qin,et al.  Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. , 2005, The Annals of thoracic surgery.

[95]  R. Mulligan,et al.  Failure of bone marrow to reconstitute lung epithelium. , 2005, American journal of respiratory cell and molecular biology.

[96]  B. Liu,et al.  Characterization and Neural Differentiation of Fetal Lung Mesenchymal Stem Cells , 2005, Cell transplantation.

[97]  J. Ingwall,et al.  Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells , 2005, Nature Medicine.

[98]  M. Pittenger,et al.  Human mesenchymal stem cells modulate allogeneic immune cell responses. , 2005, Blood.

[99]  N. Perico,et al.  Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute renal failure. , 2004, Journal of the American Society of Nephrology : JASN.

[100]  B. Burkhardt,et al.  In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. , 2004, Diabetes.

[101]  F. Claas,et al.  Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. , 2003, Blood.

[102]  W. Baumgartner,et al.  Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. , 2002, The Annals of thoracic surgery.

[103]  S. Pivina,et al.  The neonatal glucocorticoid treatment-produced long-term changes of the pituitary-adrenal function and brain corticosteroid receptors in rats , 2001, Steroids.

[104]  Peter J. Donovan,et al.  The end of the beginning for pluripotent stem cells , 2001, Nature.

[105]  N. Fisk,et al.  Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. , 2001, Blood.

[106]  F. Luyten,et al.  Multipotent mesenchymal stem cells from adult human synovial membrane. , 2001, Arthritis and rheumatism.

[107]  H. Lorenz,et al.  Multilineage cells from human adipose tissue: implications for cell-based therapies. , 2001, Tissue engineering.

[108]  S. Gronthos,et al.  Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[109]  P. Conget,et al.  Mesenchymal progenitor cells in human umbilical cord blood , 2000, British journal of haematology.

[110]  I. Weissman,et al.  Stem Cells Units of Development, Units of Regeneration, and Units in Evolution , 2000, Cell.

[111]  S. Ogawa,et al.  Cardiomyocytes can be generated from marrow stromal cells in vitro. , 1999, The Journal of clinical investigation.

[112]  John T. Williams,et al.  Cells Isolated from Adult Human Skeletal Muscle Capable of Differentiating into Multiple Mesodermal Phenotypes , 1999, The American surgeon.

[113]  P. Cony-Makhoul,et al.  Autologous blood stem cell grafting in hematological malignancies. Present status and future directions. , 1992, Transfusion science.

[114]  M. Golbus,et al.  Hematopoietic Stem Cells for the Treatment of Genetic Disease , 1986, Clinical obstetrics and gynecology.

[115]  J. Modliński.  The fate of inner cell mass and trophectoderm nuclei transplanted to fertilized mouse eggs , 1981, Nature.

[116]  N. Kulagina,et al.  Fibroblast precursors in normal and irradiated mouse hematopoietic organs. , 1976, Experimental hematology.

[117]  W. Northway,et al.  Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. , 1967, The New England journal of medicine.

[118]  M. Ericsson,et al.  Mesenchymal Stromal Cell Exosomes Ameliorate Experimental Bronchopulmonary Dysplasia and Restore Lung Function through Macrophage Immunomodulation , 2018, American journal of respiratory and critical care medicine.

[119]  H. Lee,et al.  Comparison of the anti-inflammatory effects of induced pluripotent stem cell-derived and bone marrow-derived mesenchymal stromal cells in a murine model of corneal injury. , 2017, Cytotherapy.

[120]  C. Viswanathan,et al.  Paracrine factors secreted by umbilical cord-derived mesenchymal stem cells induce angiogenesis in vitro by a VEGF-independent pathway. , 2015, Stem cells and development.

[121]  A. Hubel,et al.  Clinical mesenchymal stromal cell products undergo functional changes in response to freezing. , 2015, Cytotherapy.

[122]  K. Albertine.  Biomarkers in Lung Diseases : from Pathogenesis to Prediction to New Therapies Utility of large-animal models of BPD : chronically ventilated preterm lambs , 2015 .

[123]  K. Young,et al.  Long-term reparative effects of mesenchymal stem cell therapy following neonatal hyperoxia-induced lung injury , 2013, Pediatric Research.

[124]  Y. Chang,et al.  Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells dose-dependently attenuates hyperoxia-induced lung injury in neonatal rats. , 2011, Cell transplantation.

[125]  L. Doyle,et al.  Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. , 2009, The Cochrane database of systematic reviews.

[126]  Krisztián Németh,et al.  Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 production , 2009, Nature Medicine.

[127]  D. Prockop,et al.  Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. , 2006, Cytotherapy.

[128]  L. Monte,et al.  [Bronchopulmonary dysplasia]. , 2005, Jornal de pediatria.

[129]  M. Westphal,et al.  Stem cells in neuro-oncology--development, regeneration and treatment. , 2003, Acta neurochirurgica. Supplement.

[130]  G. Leone,et al.  Autologous peripheral blood stem cell transplantation in hematological malignancies. , 1990, Haematologica.

[131]  K. S. Lalykina,et al.  [Fibroblast-like cells in cultures of guinea pig hematopoietic tissue]. , 1970, Tsitologiia.

[132]  J. Till,et al.  A STOCHASTIC MODEL OF STEM CELL PROLIFERATION, BASED ON THE GROWTH OF SPLEEN COLONY-FORMING CELLS. , 1964, Proceedings of the National Academy of Sciences of the United States of America.