Skip to main content

Advertisement

SpringerLink
Log in

Applying the Cytocentric Principles to Regenerative Medicine for Reproducibility

  • Artificial Tissues (A Atala and J G Hunsberger, Section Editors)
  • Published:
Current Stem Cell Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Cell and tissue products do not just reflect their present conditions; they are the culmination of all they have encountered over time. Currently, routine cell culture practices subject cell and tissue products to highly variable and non-physiologic conditions. This article defines five cytocentric principles that place the conditions for cells at the core of what we do for better reproducibility in Regenerative Medicine.

Recent Findings

There is a rising awareness of the cell environment as a neglected, but critical variable. Recent publications have called for controlling culture conditions for better, more reproducible cell products.

Summary

Every industry has basic quality principles for reproducibility. Cytocentric principles focus on the fundamental needs of cells: protection from contamination, physiologic simulation, and full-time conditions for cultures that are optimal, individualized, and dynamic. Here, we outline the physiologic needs, the technologies, the education, and the regulatory support for the cytocentric principles in regenerative medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

2D:

2-Dimensional

3D:

3-Dimensional

BSC:

Biological safety cabinet

CCPs:

Critical cell parameters

ESC:

Embryonic stem cells

hiPSCs:

Human-induced pluripotent stem cells

iPSCs:

Induced pluripotent stem cells

KSA:

Knowledge, skills, and abilities

RM:

Regenerative medicine

RH:

Relative humidity

MPS:

Microphysiological system

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Baker M. 1,500 scientists lift the lid on reproducibility. Nature. 2016;533(7604):452–4.

    Article  PubMed  CAS  Google Scholar 

  2. Beachy SH, Nair L, Laurencin C, Tsokas KA, Lundberg MS. Sources of variability in clinical translation of regenerative engineering products: insights from the National Academies Forum on Regenerative Medicine. Regenerative Engineering and Translational Medicine. 2020;6(1):1–6.

    Article  CAS  Google Scholar 

  3. Klein SG, Alsolami SM, Steckbauer A, Arossa S, Parry AJ, Ramos Mandujano G, et al. A prevalent neglect of environmental control in mammalian cell culture calls for best practices. Nat Biomed Eng. 2021;5(8):787–92.

    Article  PubMed  Google Scholar 

  4. •• Klein SG, Steckbauer A, Alsolami SM, Arossa S, Parry AJ, Li M, et al. Toward best practices for controlling mammalian cell culture environments. Frontiers in Cell and Developmental Biology. 2022;10. This article calls for new processes for reporting cell culture conditions for reproducibility and offers specific guidelines.

  5. Mantel CR, O’Leary HA, Chitteti BR, Huang X, Cooper S, Hangoc G, et al. Enhancing Hematopoietic stem cell transplantation efficacy by mitigating oxygen shock. Cell. 2015;161(7):1553–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Broxmeyer HE, O’Leary HA, Huang X, Mantel C. The importance of hypoxia and extra physiologic oxygen shock/stress for collection and processing of stem and progenitor cells to understand true physiology/pathology of these cells ex vivo. Curr Opin Hematol. 2015;22(4):273–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Ast T, Mootha VK. Oxygen and mammalian cell culture: are we repeating the experiment of Dr. Ox? Nature metabolism. 2019;1(9):858–60.

  8. DiProspero TJ, Dalrymple E, Lockett MR. Physiologically relevant oxygen tensions differentially regulate hepatotoxic responses in HepG2 cells. Toxicology in vitro: an international journal published in association with BIBRA. 2021;105156.

  9. Kumar A, Dailey LA, Swedrowska M, Siow R, Mann GE, Vizcay-Barrena G, et al. Quantifying the magnitude of the oxygen artefact inherent in culturing airway cells under atmospheric oxygen versus physiological levels. FEBS Lett. 2016;590(2):258–69.

    Article  PubMed  CAS  Google Scholar 

  10. Kumar B, Adebayo AK, Prasad M, Capitano ML, Wang R, Bhat-Nakshatri P, et al. Tumor collection/processing under physioxia uncovers highly relevant signaling networks and drug sensitivity. Sci Adv. 2022;8(2):eabh3375.

  11. • Mount S, Kanda P, Parent S, Khan S, Michie C, Davila L, et al. Physiologic expansion of human heart-derived cells enhances therapeutic repair of injured myocardium. Stem Cell Res Ther. 2019;10(1):1–16. This article shows that protecting cells from uncontrolled room air during cGMP processing enhances engraftment in vivo.

  12. Anderson DE, Markway BD, Weekes KJ, McCarthy HE, Johnstone B. Physioxia promotes the articular chondrocyte-like phenotype in human chondroprogenitor-derived self-organized tissue. Tissue Eng Part A. 2018;24(3–4):264–74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Shimoni YFT, Srinivasan V, Szeto R. Reducing variability in cell-specific productivity in perfusion culture: a case study. Bioprocess International. 2018.

  14. Shimoni Y, Pathange LP. Product quality attribute shifts in perfusion systems, part 2: elucidating cellular mechanisms. BioProcess International. 2020.

  15. Gurvich OL, Puttonen KA, Bailey A, Kailaanmaki A, Skirdenko V, Sivonen M, et al. Transcriptomics uncovers substantial variability associated with alterations in manufacturing processes of macrophage cell therapy products. Sci Rep. 2020;10(1):14049.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Burke CJ, Zylberberg C. Sources of Variability in Manufacturing of Cell Therapeutics. Regenerative engineering and translational medicine. 2019;5(4):332–40.

    Article  Google Scholar 

  17. Stover AE, Herculian S, Banuelos MG, Navarro SL, Jenkins MP, Schwartz PH. Culturing human pluripotent and neural stem cells in an enclosed cell culture system for basic and preclinical research. J Vis Exp. 2016(112).

  18. Drexler HG, Dirks WG, MacLeod RA, Uphoff CC. False and mycoplasma-contaminated leukemia-lymphoma cell lines: time for a reappraisal. Int J Cancer. 2017;140(5):1209–14.

    Article  PubMed  CAS  Google Scholar 

  19. Chang Y, Goldberg VM, Caplan AI. Toxic effects of gentamicin on marrow-derived human mesenchymal stem cells. Clin Orthop Relat Res. 2006;452:242–9.

    Article  PubMed  Google Scholar 

  20. Cohen S, Samadikuchaksaraei A, Polak JM, Bishop AE. Antibiotics reduce the growth rate and differentiation of embryonic stem cell cultures. Tissue Eng. 2006;12(7):2025–30.

    Article  PubMed  CAS  Google Scholar 

  21. Jiang X, Baucom C, Elliott RL. Mitochondrial toxicity of azithromycin results in aerobic glycolysis and DNA damage of human mammary epithelia and fibroblasts. Antibiotics (Basel, Switzerland). 2019;8(3).

  22. Relier S, Yazdani L, Ayad O, Choquet A, Bourgaux JF, Prudhomme M, et al. Antibiotics inhibit sphere-forming ability in suspension culture. Cancer Cell Int. 2016;16:6.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ryu AH, Eckalbar WL, Kreimer A, Yosef N, Ahituv N. Use antibiotics in cell culture with caution: genome-wide identification of antibiotic-induced changes in gene expression and regulation. Sci Rep. 2017;7(1):7533.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Varghese DS, Parween S, Ardah MT, Emerald BS, Ansari SA. Effects of aminoglycoside antibiotics on human embryonic stem cell viability during differentiation in vitro. Stem Cells Int. 2017;2017:2451927.

    Article  PubMed  PubMed Central  Google Scholar 

  25. He Y, Darou S, Henn S, Walter R, Cundell A, Yerden R, et al. Temperature and relative humidity control to reduce bioburden in a closed cell processing and production system without disinfectants. BioPharm International. 2021.

  26. Carrel A, Lindbergh CA. The culture of organs. Am J Med Sci. 1938;196(5):732.

    Article  Google Scholar 

  27. Kleman AM, Yuan JY, Aja S, Ronnett GV, Landree LE. Physiological glucose is critical for optimized neuronal viability and AMPK responsiveness in vitro. J Neurosci Methods. 2008;167(2):292–301.

    Article  PubMed  CAS  Google Scholar 

  28. Davidson MD, Pickrell J, Khetani SR. Physiologically inspired culture medium prolongs the lifetime and insulin sensitivity of human hepatocytes in micropatterned co-cultures. Toxicology. 2021;449: 152662.

    Article  PubMed  CAS  Google Scholar 

  29. Moradi F, Moffatt C, Stuart JA. The effect of oxygen and micronutrient composition of cell growth media on cancer cell bioenergetics and mitochondrial networks. Biomolecules. 2021;11(8):1177.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Rogers LK, Cismowski MJ. Oxidative stress in the lung - the essential paradox. Current opinion in toxicology. 2018;7:37–43.

    Article  PubMed  Google Scholar 

  31. Keeley TP, Mann GE. Defining physiological normoxia for improved translation of cell physiology to animal models and humans. Physiol Rev. 2019;99(1):161–234.

    Article  PubMed  CAS  Google Scholar 

  32. Carreau A, El Hafny-Rahbi B, Matejuk A, Grillon C, Kieda C. Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia. J Cell Mol Med. 2011;15(6):1239–53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Wenger RH, Kurtcuoglu V, Scholz CC, Marti HH, Hoogewijs D. Frequently asked questions in hypoxia research. Hypoxia. 2015;3:35–43.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Bambrick L, Kostov Y, Rao G. In vitro cell culture pO2 is significantly different from incubator pO2. Biotechnol Prog. 2011;27(4):1185–9.

    Article  PubMed  CAS  Google Scholar 

  35. Mohyeldin A, Garzon-Muvdi T, Quinones-Hinojosa A. Oxygen in stem cell biology: a critical component of the stem cell niche. Cell Stem Cell. 2010;7(2):150–61.

    Article  PubMed  CAS  Google Scholar 

  36. Shariati L, Esmaeili Y, Javanmard SH, Bidram E, Amini A. Organoid technology: current standing and future perspectives. Stem Cells. 2021.

  37. Bannier-Helaouet M, Post Y, Korving J, Trani Bustos M, Gehart H, Begthel H, et al. Exploring the human lacrimal gland using organoids and single-cell sequencing. Cell Stem Cell. 2021.

  38. Li Q, Qi G, Liu X, Bai J, Zhao J, Tang G, et al. Universal peptide hydrogel for scalable physiological formation and bioprinting of 3D spheroids from human induced pluripotent stem cells. Adv Funct Mater. 2021;31(41):2104046.

  39. Lehmann R, Lee CM, Shugart EC, Benedetti M, Charo RA, Gartner Z, et al. Human organoids: a new dimension in cell biology. Mol Biol Cell. 2019;30(10):1129–37.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Kim J, Koo B-K, Knoblich JA. Human organoids: model systems for human biology and medicine. Nat Rev Mol Cell Biol. 2020;21(10):571–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Thippabhotla S, Zhong C, He M. 3D cell culture stimulates the secretion of in vivo like extracellular vesicles. Sci Rep. 2019;9(1):1–14.

    Article  CAS  Google Scholar 

  42. Fioretta ES, Simonet M, Smits AI, Baaijens FP, Bouten CV. Differential response of endothelial and endothelial colony forming cells on electrospun scaffolds with distinct microfiber diameters. Biomacromol. 2014;15(3):821–9.

    Article  CAS  Google Scholar 

  43. Wright Muelas M, Ortega F, Breitling R, Bendtsen C, Westerhoff HV. Rational cell culture optimization enhances experimental reproducibility in cancer cells. Sci Rep. 2018;8(1):3029.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Tse HM, Gardner G, Dominguez-Bendala J, Fraker CA. The importance of proper oxygenation in 3D culture. Front Bioeng Biotechnol. 2021;9(241): 634403.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Wohlrab P, Johann Danhofer M, Schaubmayr W, Tiboldi A, Krenn K, Markstaller K, et al. Oxygen conditions oscillating between hypoxia and hyperoxia induce different effects in the pulmonary endothelium compared to constant oxygen conditions. Physiol Rep. 2021;9(3): e14590.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Shin DY, Huang X, Gil CH, Aljoufi A, Ropa J, Broxmeyer HE. Physioxia enhances T-cell development ex vivo from human hematopoietic stem and progenitor cells. Stem Cells. 2020

  47. Sagan DS, Carl Margulis L. Life. Encyclopedia Britannica 2020

  48. Hofer M, Lutolf MP. Engineering organoids. Nat Rev Mater. 2021;1–19.

  49. Bhatia SN, Ingber DE. Microfluidic organs-on-chips. Nat Biotechnol. 2014;32(8):760–72.

    Article  PubMed  CAS  Google Scholar 

  50. Kimura H, Sakai Y, Fujii T. Organ/body-on-a-chip based on microfluidic technology for drug discovery. Drug Metab Pharmacokinet. 2018;33(1):43–8.

    Article  PubMed  CAS  Google Scholar 

  51. Yang Q, Lian Q, Xu F. Perspective: fabrication of integrated organ-on-a-chip via bioprinting. Biomicrofluidics. 2017;11(3): 031301.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Yesil-Celiktas O, Hassan S, Miri AK, Maharjan S, Al-kharboosh R, Quiñones-Hinojosa A, et al. Mimicking human pathophysiology in organ-on-chip devices. Advanced Biosystems. 2018;2(10):1800109.

    Article  Google Scholar 

  53. Zhang B, Radisic M. Organ-on-a-chip devices advance to market. Lab Chip. 2017;17(14):2395–420.

    Article  PubMed  CAS  Google Scholar 

  54. Zhang YS, Aleman J, Shin SR, Kilic T, Kim D, Mousavi Shaegh SA, et al. Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. Proc Natl Acad Sci U S A. 2017;114(12):E2293–302.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Aleman J, Kilic T, Mille LS, Shin SR, Zhang YS. Microfluidic integration of regeneratable electrochemical affinity-based biosensors for continual monitoring of organ-on-a-chip devices. Nat Protoc. 2021;16(5):2564–93.

    Article  PubMed  CAS  Google Scholar 

  56. Duzagac F, Saorin G, Memeo L, Canzonieri V, Rizzolio F. Microfluidic organoids-on-a-chip: quantum leap in cancer research. Cancers (Basel). 2021;13(4):737.

    Article  Google Scholar 

  57. Matsui TK, Tsuru Y, Hasegawa K, Kuwako KI. Vascularization of human brain organoids. Stem Cells. 2021

  58. Osaki T, Sivathanu V, Kamm RD. Vascularized microfluidic organ-chips for drug screening, disease models and tissue engineering. Curr Opin Biotechnol. 2018;52:116–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Park SE, Georgescu A, Huh D. Organoids-on-a-chip Science. 2019;364(6444):960–5.

    PubMed  CAS  Google Scholar 

  60. Ingber DE. Reverse engineering human pathophysiology with organs-on-chips. Cell. 2016;164(6):1105–9.

    Article  PubMed  CAS  Google Scholar 

  61. Esch MB, King TL, Shuler ML. The role of body-on-a-chip devices in drug and toxicity studies. Annu Rev Biomed Eng. 2011;13:55–72.

    Article  PubMed  CAS  Google Scholar 

  62. Skardal A, Shupe T, Atala A. Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling. Drug Discov Today. 2016;21(9):1399–411.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Novak R, Ingram M, Marquez S, Das D, Delahanty A, Herland A, et al. Robotic fluidic coupling and interrogation of multiple vascularized organ chips. Nat Biomed Eng. 2020;4(4):407–20.

    Article  PubMed  PubMed Central  Google Scholar 

  64. McAleer CW, Long CJ, Elbrecht D, Sasserath T, Bridges LR, Rumsey JW, et al. Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics. Sci Transl Med. 2019;11(497).

  65. ISO 13408–1. Aseptic processing of health care products - Part 1: general Requirements. 2008.

  66. ISO 13408–2. Aseptic processing of health care products - Part 2: sterilizing filtration. 2018.

  67. ISO 13408–3. Aseptic processing of health care products - Part 3: lyophilization. 2006.

  68. ISO 13408–4. Aseptic processing of health care products - Part 4: clean-in-place technologies. 2005.

  69. ISO 13408–5. Aseptic processing of health care products - Part 5: sterilization in place. 2005.

  70. ISO 13408–6. Aseptic processing of health care products - Part 6: isolator systems. 2005.

  71. ISO 13408–7. Aseptic processing of health care products - Part 7: alternative processes for medical devices and combination productsISO 14644–1 Cleanrooms and associated controlled environments - Part 1: classification of air cleanliness by particle concentration. 2012.

  72. ISO 14644–1. Cleanrooms and associated controlled environments - Part 1: classification of air cleanliness by particle concentration. 2015.

  73. ISO 14644–2. Cleanrooms and associated controlled environments - Part 2: monitoring to provide evidence of cleanroom performance related to air cleanliness by particle concentration. In: Inte, editor. 2015.

  74. ISO 14644–3. Cleanrooms and associated controlled environments - Part 3: test methods2019.

  75. ISO 14644–4. Cleanrooms and associated controlled environments - Part 4: design, construction and start-up. 2001.

  76. ISO 14644–5. Cleanrooms and associated controlled environments - Part 5: operations. 2004.

  77. ISO 14644–7. Cleanrooms and associated controlled environments - Part 7: separative devices (clean air hoods, gloveboxes, isolators and mini-environments). 2004.

  78. ISO 14644–8. Cleanrooms and associated controlled environments - Part 8: classification of air cleanliness by chemical concentration (ACC). 2013.

  79. ISO 14644–9. Cleanrooms and associated controlled environments - Part 9: classification of surface cleanliness by particle concentration. 2012.

  80. ISO 14644–10. Cleanrooms and associated controlled environments - Part 10: classification of surface cleanliness by chemical concentration. 2013.

  81. ISO 14644–13. Cleanrooms and associated controlled environments - Part 13: cleaning of surfaces to achieve defined levels of cleanliness in terms of particle and chemical classifications. 2017.

  82. ISO 14644–14. Cleanrooms and associated controlled environments - Part 14: assessment of suitability for use of equipment by airborne particle concentration. 2016.

  83. ISO 14644–15. Cleanrooms and associated controlled environments - Part 15: assessment of suitability for use of equipment and materials by airborne chemical concentration. 2017.

  84. ISO 14698–1. Cleanrooms and associated controlled environments - biocontamination control Part 1: general principles and methods. 2003.

  85. ISO 14698–2. Cleanrooms and associated controlled environments - biocontamination control Part 2: evaluation and interpretation of biocontamination data. 2003.

  86. • Green GM, Read RH, Lee S, Tubon T, Hunsberger JG, Atala A. Recommendations for workforce development in regenerative medicine biomanufacturing. Stem Cells Transl Med. 2021.

  87. Ioannidis JP. Why most published research findings are false. PLoS Med. 2005;2(8):e124.

  88. Al-Ani A, Toms D, Kondro D, Thundathil J, Yu Y, Ungrin M. Oxygenation in cell culture: critical parameters for reproducibility are routinely not reported. PLoS ONE. 2018;13(10): e0204269.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Michl J, Park KC, Swietach P. Evidence-based guidelines for controlling pH in mammalian live-cell culture systems. Communications biology. 2019;2:144.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Refresh cell culture. Nat Biomed Eng. 2021;5(8):783–4.

    Article  Google Scholar 

  91. Nießing B, Kiesel R, Herbst L, Schmitt RH. Techno-economic analysis of automated iPSC production. Processes. 2021;9(2):240.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Ray Gould, Stassa P.D. Henn, and Shannon Darou for their critical reading of the manuscript.

This manuscript represents the opinions of the authors and may not represent the positions of NIST, people mentioned in the acknowledgments, or any other organization. Certain equipment, instruments, or materials are identified in this paper to adequately specify the experimental details. Such identification does not imply a recommendation by NIST, nor does it imply the materials are necessarily the best available for the purpose. This manuscript is a contribution of NIST and therefore is not subject to copyright in the USA.

Author information

Authors and Affiliations

  1. BioSpherix, Ltd, 25 Union St, Parish, NY, 13131, USA

    Alicia D. Henn & Randy Yerden

  2. Biomedical Engineering, Florida Institute of Technology, Melbourne, FL, USA

    Kunal Mitra

  3. RegenMed Development Organization, Winston-Salem, NC, USA

    Joshua Hunsberger & Gary Green

  4. Kansas State University, Manhattan, KS, USA

    Xiuzhi Susan Sun

  5. Bio-Trac, Germantown, MD, USA

    Mark Nardone

  6. Akron Biotech, Boca Raton, FL, USA

    Ramon Montero

  7. RTI International, Durham, NC, USA

    Sita Somara

  8. Thrive Bioscience, Beverly, MA, USA

    Alan Blanchard

  9. Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA, USA

    Yu Shrike Zhang

  10. Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA

    Carl G. Simon

Authors
  1. Alicia D. Henn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kunal Mitra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joshua Hunsberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiuzhi Susan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mark Nardone
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ramon Montero
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sita Somara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gary Green
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alan Blanchard
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yu Shrike Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Carl G. Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Randy Yerden
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors discussed the contents and participated in writing the manuscript. AH handled final editing.

Corresponding author

Correspondence to Alicia D. Henn.

Ethics declarations

Conflict of Interest

Alicia Henn, Xiuzhi Susan Sun, Mark Nardone, Ramon Montero, Alan Blanchard, and Randy Yerden are employed by for-profit companies (eg, BioSpherix, Akron Biotech, Thrive Bioscience) working to advance regenerative medicine and so have a financial interest. Kunal Mitra, Joshua Hunsberger, Sita Somara, Gary Green, and Carl G. Simon, Jr. declare that they have no conflict of interest. 

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This articleis part of Topical Collection on Artificial Tissues

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Henn, A.D., Mitra, K., Hunsberger, J. et al. Applying the Cytocentric Principles to Regenerative Medicine for Reproducibility. Curr Stem Cell Rep 8, 197–205 (2022). https://doi.org/10.1007/s40778-022-00219-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40778-022-00219-8

Keywords

Search

Navigation