Qualifying stem cell sources: how to overcome potential pitfalls in regenerative medicine?

Regenerative medicine aims to replace lost cells and to restore damaged tissues and organs by either tissue‐engineering approaches or stimulation of endogenous processes. Due to their biological properties, stem cells promise to be an effective source for such strategies. Especially adult multipotent stem cells (ASCs) are believed to be applicable in a broad range of therapies for the treatment of multifactorial diseases or age‐related degeneration, although the molecular and cellular mechanisms underlying their regenerative function are often hardly described. Moreover, in some demanding clinical situations their efficiency remains limited. Thus, a basic understanding of ASCs regenerative function, their complex interplay with their microenvironment and how compromising conditions interfere with their efficiency is mandatory for any regenerative strategy. Concerning this matter, the impact of patient‐specific constraints are often underestimated in research projects and their influence on the study results disregarded. Thus, researchers are urgently depending on well‐characterized tissue samples or cells that are connected with corresponding donor information, such as secondary diseases, medication. Here, we outline principle pitfalls during experimental studies using human samples, and describe a potential strategy to overcome these challenges by establishing a core unit for cell and tissue harvesting. This facility aims to bridge the gap between clinic and research laboratories by the provision of a direct link to the clinical operating theatres. Such a strategy clearly supports basic and clinical research in the conduct of their studies and supplies highly characterized human samples together with the corresponding donor information. Copyright © 2014 John Wiley & Sons, Ltd.

[1]  M. Genovese,et al.  COX‐2 selective NSAID decreases bone ingrowth in vivo , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[2]  G. Duda,et al.  Matrix Metalloprotease Activity Is an Essential Link Between Mechanical Stimulus and Mesenchymal Stem Cell Behavior , 2007, Stem cells.

[3]  Hsu-hsin Chen,et al.  An ES-Like Pluripotent State in FGF-Dependent Murine iPS cells , 2010, PloS one.

[4]  I. Weissman,et al.  Rejuvenation of aged progenitor cells by exposure to a young systemic environment , 2005, Nature.

[5]  C. Coleman,et al.  How do we know that research ethics committees are really working? The neglected role of outcomes assessment in research ethics review , 2008, BMC medical ethics.

[6]  Min Zhu,et al.  Human adipose tissue is a source of multipotent stem cells. , 2002, Molecular biology of the cell.

[7]  E. Hofer,et al.  Bone marrow fibroblasts in patients with advanced lung cancer. , 2001, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[8]  Regina Brunauer,et al.  Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan , 2007, Aging cell.

[9]  B. Bilican,et al.  Neural Precursor Cells Cultured at Physiologically Relevant Oxygen Tensions Have a Survival Advantage Following Transplantation , 2013, Stem cells translational medicine.

[10]  Hermann Eichler,et al.  Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue , 2006, Stem cells.

[11]  E. Eftekharpour,et al.  Stem cells and spinal cord injury repair. , 2012, Advances in experimental medicine and biology.

[12]  J. Piek,et al.  Recovery and functional activity of mononuclear bone marrow and peripheral blood cells after different cell isolation protocols used in clinical trials for cell therapy after acute myocardial infarction. , 2008, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[13]  V. L. La Russa,et al.  Mesenchymal stromal cells, colony-forming unit fibroblasts, from bone marrow of untreated advanced breast and lung cancer patients suppress fibroblast colony formation from healthy marrow. , 2010, Stem cells and development.

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

[15]  K. Park,et al.  Neural stem cells: properties and therapeutic potentials for hypoxic‐ischemic brain injury in newborn infants , 2010, Pediatrics international : official journal of the Japan Pediatric Society.

[16]  S. Perez,et al.  Characterization of the Optimal Culture Conditions for Clinical Scale Production of Human Mesenchymal Stem Cells , 2006, Stem cells.

[17]  Robert S Negrin,et al.  Hematopoietic stem and progenitor cells: clinical and preclinical regeneration of the hematolymphoid system. , 2005, Annual review of medicine.

[18]  J. Rodríguez,et al.  Mesenchymal stem cells from osteoporotic patients produce a type I collagen‐deficient extracellular matrix favoring adipogenic differentiation , 2000, Journal of cellular biochemistry.

[19]  C. Chiu,et al.  Hypoxia inhibits senescence and maintains mesenchymal stem cell properties through down-regulation of E2A-p21 by HIF-TWIST. , 2011, Blood.

[20]  L. Schiff Review: Production, characterization, and testing of banked mammalian cell substrates used to produce biological products , 2005, In Vitro Cellular & Developmental Biology - Animal.

[21]  P. Tiberghien,et al.  Human and rodent bone marrow mesenchymal stem cells that express primitive stem cell markers can be directly enriched by using the CD49a molecule , 2007, Cell and Tissue Research.

[22]  Robert C. Wolpert,et al.  A Review of the , 1985 .

[23]  Andrew Scutt,et al.  Aging of mesenchymal stem cells , 2006, Ageing Research Reviews.

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

[25]  Navrag B. Singh,et al.  Terminally Differentiated CD8+ T Cells Negatively Affect Bone Regeneration in Humans , 2013, Science Translational Medicine.

[26]  Y. Kato,et al.  Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF. , 2001, Biochemical and biophysical research communications.

[27]  E. Marbán,et al.  Physiological Levels of Reactive Oxygen Species Are Required to Maintain Genomic Stability in Stem Cells , 2010, Stem cells.

[28]  E. Horwitz Advancing Regenerative Medicine the Translational Way , 2013, Science Translational Medicine.

[29]  R. Bjerkvig,et al.  Spontaneous malignant transformation of human mesenchymal stem cells reflects cross-contamination: putting the research field on track - letter. , 2010, Cancer research.

[30]  J. V. van Delden,et al.  Inclusion of Residual Tissue in Biobanks: Opt-In or Opt-Out? , 2012, PLoS biology.

[31]  R. Poulsom,et al.  An introduction to stem cells , 2002, The Journal of pathology.

[32]  J. Lebkowski,et al.  Serum‐free culture of hematopoietic stem cells: A Review , 1995, Stem cells.

[33]  C. Kahn,et al.  Endocrine regulation of ageing , 2007, Nature Reviews Molecular Cell Biology.

[34]  W. Taylor,et al.  Modulation of matrix metalloprotease-2 levels by mechanical loading of three-dimensional mesenchymal stem cell constructs: impact on in vitro tube formation. , 2010, Tissue engineering. Part A.

[35]  P. Rameshwar,et al.  Oxygen saturation in the bone marrow of healthy volunteers. , 2002, Blood.

[36]  J. Rodríguez,et al.  Abnormal osteogenesis in osteoporotic patients is reflected by altered mesenchymal stem cells dynamics , 1999, Journal of cellular biochemistry.

[37]  A. Wagers,et al.  No place like home: anatomy and function of the stem cell niche , 2008, Nature Reviews Molecular Cell Biology.

[38]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[39]  Mayasari Lim,et al.  Stem cell bioprocessing: fundamentals and principles , 2009, Journal of The Royal Society Interface.

[40]  E. Thomas,et al.  Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. , 1957, The New England journal of medicine.

[41]  Ronald A. DePinho,et al.  How stem cells age and why this makes us grow old , 2007, Nature Reviews Molecular Cell Biology.

[42]  G. Duda,et al.  Mesenchymal Stem Cells Regulate Angiogenesis According to Their Mechanical Environment , 2007, Stem cells.

[43]  Masayo Katano,et al.  Quality control and monitoring for the isolation process of mesenchymal stem cells and their differentiation into osteoblasts. , 2010, Genetic testing and molecular biomarkers.

[44]  G. Duda,et al.  Functional Comparison of Chronological and In Vitro Aging: Differential Role of the Cytoskeleton and Mitochondria in Mesenchymal Stromal Cells , 2012, PloS one.

[45]  Sanjay Kumar,et al.  Therapeutic potential of adult bone marrow‐derived mesenchymal stem cells in diseases of the skeleton , 2010, Journal of cellular biochemistry.

[46]  A. Simpson,et al.  Physiologic oxygen enhances human embryonic stem cell clonal recovery and reduces chromosomal abnormalities. , 2006, Cloning and stem cells.

[47]  A. Scutt,et al.  Glucose-induced replicative senescence in mesenchymal stem cells. , 2006, Rejuvenation research.

[48]  C. Zhang,et al.  Hypoxia and metabolic properties of hematopoietic stem cells. , 2014, Antioxidants & redox signaling.

[49]  M. Lindberg,et al.  Adipose Tissue , 2018 .

[50]  J. Bassett,et al.  The molecular actions of thyroid hormone in bone , 2003, Trends in Endocrinology & Metabolism.

[51]  A. Rizvi,et al.  Epithelial Stem Cells and Their Niche: There's No Place Like Home , 2005, Stem cells.

[52]  Y. Kim,et al.  The effects of COX-2 inhibitor during osteogenic differentiation of bone marrow-derived human mesenchymal stem cells. , 2010, Stem cells and development.

[53]  J. Adjaye,et al.  Human skin stem cells and the ageing process , 2008, Experimental Gerontology.

[54]  Gang Li,et al.  Nonsteroidal anti-inflammatory drug-induced fracture nonunion: an inhibition of angiogenesis? , 2006, The Journal of bone and joint surgery. American volume.

[55]  G. Duda,et al.  Insights into Mesenchymal Stem Cell Aging: Involvement of Antioxidant Defense and Actin Cytoskeleton , 2009, Stem cells.

[56]  C. Lengerke,et al.  Patient-specific pluripotent stem cells: promises and challenges , 2009, Nature Reviews Endocrinology.

[57]  A. Gajić,et al.  The international quality requirements for the conduct of clinical studies and the challenges for study centers to implement them. , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[58]  H. Lehrach,et al.  Fibroblast Growth Factor 2 Modulates Transforming Growth Factor β Signaling in Mouse Embryonic Fibroblasts and Human ESCs (hESCs) to Support hESC Self‐Renewal , 2007, Stem cells.

[59]  C. Grady Do IRBs protect human research participants? , 2010, JAMA.

[60]  C. Viswanathan,et al.  Establishment of a Mesenchymal Stem Cell Bank , 2011, Stem cells international.

[61]  정광수,et al.  Neural stem cells: properties and therapeutic potentials for hypoxic-ischemic brain injury in newborn infants , 2010 .

[62]  H. Klüter,et al.  Human AB Serum and Thrombin‐Activated Platelet‐Rich Plasma Are Suitable Alternatives to Fetal Calf Serum for the Expansion of Mesenchymal Stem Cells from Adipose Tissue , 2007, Stem cells.

[63]  D J Prockop,et al.  Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[64]  Yu Xin Wang,et al.  Satellite cells, the engines of muscle repair , 2011, Nature Reviews Molecular Cell Biology.

[65]  T. Rando Stem cells, ageing and the quest for immortality , 2006, Nature.

[66]  Daniel-Christoph Wagner,et al.  Density Gradient Centrifugation Compromises Bone Marrow Mononuclear Cell Yield , 2012, PloS one.