Skip to main content
SpringerLink
Log in

Stem Cell Aging and Regenerative Medicine

  • Chapter
  • First Online:
Cell Biology and Translational Medicine, Volume 12

Part of the book series: Advances in Experimental Medicine and Biology ((CBTMED,volume 1326))

Abstract

Stem cells are a promising source for regenerative medicine to cure a plethora of diseases that are currently treated based on either palliative or symptomatic relief or by preventing their onset and progression. Aging-associated degenerative changes in stem cells, stem cell niches, and signaling pathways bring a step by step decline in the regenerative and functional potential of tissues. Clinical studies and experiments on model organisms have pointed out checkpoints that aging will inevitably impose on stem cell aiming for transplantation and hence questions are raised about the age of the donor. In the following discourse, we review the fundamental molecular pathways that are implicated in stem cell aging and the current progress in tissue engineering and transplantation of each type of stem cells in regenerative medicine. We further focus on the consequences of stem cell aging on their clinical uses and the development of novel strategies to bypass those pitfalls and improve tissue replenishment.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ADSC:

Adipose tissue-derived stem cell

ASC:

Adult stem cell

BMSC/BMDSC:

Bone marrow-derived mesenchymal stem/stromal cell

CSC:

Cardiac stem cell

DNMT:

DNA methyltransferase

EPC:

Endothelial progenitor cell

ESC:

Embryonic stem cell

G-CSF:

Granulocyte colony-stimulating factor

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

GSC:

Germline stem cell

GVHD:

Graft versus host disease

HAT:

Histone acetyltransferase

HDAC:

Histone deacetylase

HIF:

Hypoxia-Inducible Factor

HSC:

Haematopoietic stem cell

ICM:

Inner cell mass

iPSC:

Induced pluripotent stem cell

ISC:

Intestinal stem cell

LDHA:

Lactate dehydrogenase A

MDSC:

Muscle-derived stem cell

MSC:

Mesenchymal stem cell

NAC:

N-acetylcysteine

NHEJ:

Non-homologous end joining

NPC:

Neural precursor cell

NSC:

Neural stem cell

PDK:

Pyruvate dehydrogenase kinase

PNPase:

Polynucleotide Phosphorylase

ROS:

Reactive oxygen species

SASP:

Senescence-associated secretory phenotype

SC:

Stem cell

SCNT:

Somatic cell nuclear transfer

SGZ:

Subgranular zone

SSC:

Skin stem cell

SVZ:

Subventricular zone

TERT:

Telomerase Reverse Transcriptase

UCB:

Umbilical cord blood

References

  • Abelson S, Wang J (2018) Age-related clonal hematopoiesis. Curr Opin Hematol 25(6):441–445

    Article  PubMed  Google Scholar 

  • Adams P, Jasper H, Rudolph K (2015) Aging-induced stem cell mutations as drivers for disease and cancer. Cell Stem Cell 16(6):601–612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adiwinata PJ (2019) Exploring the Most promising stem cell therapy in liver failure: a systematic review. Stem Cells Int 2019:1–15

    Article  CAS  Google Scholar 

  • Al zouabi L, Bardin A (2020) Stem cell DNA damage and genome mutation in the context of aging and cancer initiation. Cold Spring Harb Perspect Biol:a036210. https://doi.org/10.1101/cshperspect.a036210

  • Azuma E, Hirayama M, Yamamoto H, Komada Y (2002) The role of donor age in naive T-cell recovery following allogeneic hematopoietic stem cell transplantation: the younger the better. Leuk Lymphoma 43(4):735–739

    Article  PubMed  Google Scholar 

  • Baharvand H, Jafary H, Massumi M, Ashtiani S (2006) Generation of insulin-secreting cells from human embryonic stem cells. Dev Growth Differ 48(5):323–332

    Article  CAS  PubMed  Google Scholar 

  • Bajada S, Mazakova I, Richardson JB, Ashammakhi N (2008) Updates on stem cells and their applications in regenerative medicine. J Tissue Eng Regen Med 2(4):169–183

    Article  CAS  PubMed  Google Scholar 

  • Beerman I, Rossi D (2015) Epigenetic control of stem cell potential during homeostasis, aging, and disease. Cell Stem Cell 16(6):613–625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Behrens A, van Deursen J, Rudolph K, Schumacher B (2014) Impact of genomic damage and ageing on stem cell function. Nat Cell Biol 16(3):201–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beltrami A, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S et al (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114(6):763–776

    Article  CAS  PubMed  Google Scholar 

  • Bigarella C, Liang R, Ghaffari S (2014) Stem cells and the impact of ROS signaling. Development 141(22):4206–4218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blasco M (2007) Telomere length, stem cells and aging. Nat Chem Biol 3(10):640–649

    Article  CAS  PubMed  Google Scholar 

  • Boheler KR, Czyz J, Tweedie D, Yang H-T, Anisimov SV, Wobus AM (2002) Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ Res 91(3):189–201

    Article  CAS  PubMed  Google Scholar 

  • Bonner-Weir S, Toschi E, Inada A, Reitz P, Fonseca S, Aye T et al (2004) The pancreatic ductal epithelium serves as a potential pool of progenitor cells. Pediatr Diabetes 5(s2):16–22

    Article  PubMed  Google Scholar 

  • Brown J, Weissman I (2004) Progress and prospects in hematopoietic stem cell expansion and transplantation. Exp Hematol 32(8):693–695

    Article  CAS  PubMed  Google Scholar 

  • Brunet A, Rando T (2017) Interaction between epigenetic and metabolism in aging stem cells. Curr Opin Cell Biol 45:1–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Charif N, Li Y, Targa L, Zhang L, Ye J, Li Y et al (2017) Aging of bone marrow mesenchymal stromal/stem cells: implications on autologous regenerative medicine. Biomed Mater Eng 28(s1):S57–S63

    CAS  PubMed  Google Scholar 

  • Choudhary B (2012) Telomere and telomerase in stem cells relevance in ageing and disease. Front Biosci S4(1):16–30

    Article  CAS  Google Scholar 

  • Conboy I, Conboy M, Wagers A, Girma E, Weissman I, Rando T (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433(7027):760–764

    Article  CAS  PubMed  Google Scholar 

  • Doğan A (2018) Embryonic stem cells in development and regenerative medicine. Adv Exp Med Biol 1079:1–15

    Article  PubMed  CAS  Google Scholar 

  • Dufrane D (2017) Impact of age on human adipose stem cells for bone tissue engineering. Cell Transplant 26(9):1496–1504

    Article  PubMed  PubMed Central  Google Scholar 

  • García-Prat L, Sousa-Victor P, Muñoz-Cánoves P (2017) Proteostatic and metabolic control of stemness. Cell Stem Cell 20(5):593–608

    Article  PubMed  CAS  Google Scholar 

  • Herrera M, Bruno S, Buttiglieri S, Tetta C, Gatti S, Deregibus M et al (2006) Isolation and characterization of a stem cell population from adult human liver. Stem Cells 24(12):2840–2850

    Article  CAS  PubMed  Google Scholar 

  • Horwitz E, Prockop D, Fitzpatrick L, Koo W, Gordon P, Neel M et al (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5(3):309–313

    Article  CAS  PubMed  Google Scholar 

  • Insinga A, Cicalese A, Pelicci P (2014) DNA damage response in adult stem cells. Blood Cell Mol Dis 52(4):147–151

    Article  CAS  Google Scholar 

  • Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman P, Mar B et al (2014) Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 371(26):2488–2498

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ju Z, Rudolph L (2008) Telomere dysfunction and stem cell ageing. Biochimie 90(1):24–32

    Article  CAS  PubMed  Google Scholar 

  • Kenyon J, Gerson S (2007) The role of DNA damage repair in aging of adult stem cells. Nucleic Acids Res 35(22):7557–7565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan F, Almohazey D, Alomari M, Almofty S (2018) Isolation, culture, and functional characterization of human embryonic stem cells: current trends and challenges. Stem Cells Int 2018:1–8

    Article  CAS  Google Scholar 

  • Kind A, Colman A (1999) Therapeutic cloning: needs and prospects. Semin Cell Dev Biol 10(3):279–286

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi C, Suda T (2011) Regulation of reactive oxygen species in stem cells and cancer stem cells. J Cell Physiol 227(2):421–430

    Article  CAS  Google Scholar 

  • Koenig S, Krause P, Drabent B, Schaeffner I, Christ B, Schwartz P et al (2006) The expression of mesenchymal, neural and haematopoietic stem cell markers in adult hepatocytes proliferating in vitro. J Hepatol 44(6):1115–1124

    Article  CAS  PubMed  Google Scholar 

  • Kornicka K, Marycz K, Tomaszewski K, Marędziak M, Śmieszek A (2015) The effect of age on osteogenic and adipogenic differentiation potential of Human Adipose Derived Stromal Stem Cells (hASCs) and the impact of stress factors in the course of the differentiation process. Oxidative Med Cell Longev 2015:1–20

    Article  Google Scholar 

  • Krampera M, Pizzolo G, Aprili G, Franchini M (2006) Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair. Bone 39(4):678–683

    Article  CAS  PubMed  Google Scholar 

  • Krauss S, de Haan G (2016) Epigenetic perturbations in aging stem cells. Mamm Genome 27(7–8):396–406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuo C, Li W, Mauck R, Tuan R (2006) Cartilage tissue engineering: its potential and uses. Curr Opin Rheumatol 18(1):64–73

    Article  PubMed  Google Scholar 

  • Lau A, Kennedy B, Kirkland J, Tullius S (2019) Mixing old and young: enhancing rejuvenation and accelerating aging. J Clin Investig 129(1):4–11

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee H, Gutierrez-Garcia R, Vilchez D (2016) Embryonic stem cells: a novel paradigm to study proteostasis? FEBS J 284(3):391–398

    Article  PubMed  CAS  Google Scholar 

  • Liang R, Ghaffari S (2014) Stem cells, redox signaling, and stem cell aging. Antioxid Redox Signal 20(12):1902–1916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lindvall O, Kokaia Z, Martinez-Serrano A (2004) Stem cell therapy for human neurodegenerative disorders–how to make it work. Nat Med 10(S7):S42–S50

    Article  PubMed  CAS  Google Scholar 

  • Liu L, Rando T (2011) Manifestations and mechanisms of stem cell aging. J Cell Biol 193(2):257–266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lo Sardo V, Ferguson W, Erikson G, Topol E, Baldwin K, Torkamani A (2016) Influence of donor age on induced pluripotent stem cells. Nat Biotechnol 35(1):69–74

    Article  PubMed  CAS  Google Scholar 

  • Martino G, Pluchino S (2006) The therapeutic potential of neural stem cells. Nat Rev Neurosci 7(5):395–406

    Article  CAS  PubMed  Google Scholar 

  • McArdle A, Senarath-Yapa K, Walmsley G, Hu M, Atashroo D, Tevlin R et al (2014) The role of stem cells in aesthetic surgery. Plast Reconstr Surg 134(2):193–200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McNeely T, Leone M, Yanai H, Beerman I (2019) DNA damage in aging, the stem cell perspective. Hum Genet 139(3):309–331

    Article  PubMed  PubMed Central  Google Scholar 

  • Miller MQ, Dighe A, Cui Q, Park SS, Christophel JJ (2016) Regenerative medicine in facial plastic and reconstructive surgery. JAMA Facial Plast Surg 18(5):391

    Article  PubMed  Google Scholar 

  • Min-Wen J, Jun-Hao E, Shyh-Chang N (2016) Stem cell mitochondria during aging. Semin Cell Dev Biol 52:110–118

    Article  CAS  PubMed  Google Scholar 

  • Müller A, Huppertz S, Henschler R (2016) Hematopoietic stem cells in regenerative medicine: astray or on the path? Transfus Med Hemother 43(4):247–254

    Article  PubMed  PubMed Central  Google Scholar 

  • Müller P, Lemcke H, David R (2018) Stem cell therapy in heart diseases – cell types, mechanisms and improvement strategies. Cell Physiol Biochem 48(6):2607–2655

    Article  PubMed  CAS  Google Scholar 

  • Nakao K, Tsuji T (2008) Dental regenerative therapy: stem cell transplantation and bioengineered tooth replacement. Jpn Dent Sci Rev 44(1):70–75

    Article  Google Scholar 

  • Noormohammadi A, Calculli G, Gutierrez-Garcia R, Khodakarami A, Koyuncu S, Vilchez D (2017) Mechanisms of protein homeostasis (proteostasis) maintain stem cell identity in mammalian pluripotent stem cells. Cell Mol Life Sci 75(2):275–290

    Article  PubMed  CAS  Google Scholar 

  • Nowacki M, Kloskowski T, Pokrywczyńska M, Nazarewski Ł, Jundziłł A, Pietkun K et al (2014) Is regenerative medicine a new hope for kidney replacement? J Artif Organs 17(2):123–134

    Article  PubMed  Google Scholar 

  • Nuschke A (2013) Activity of mesenchymal stem cells in therapies for chronic skin wound healing. Organogenesis 10(1):29–37

    Article  PubMed  PubMed Central  Google Scholar 

  • Nussler A, Konig S, Ott M, Sokal E, Christ B, Thasler W et al (2006) Present status and perspectives of cell-based therapies for liver diseases. J Hepatol 45(1):144–159

    Article  CAS  PubMed  Google Scholar 

  • Qu-Petersen Z, Deasy B, Jankowski R, Ikezawa M, Cummins J, Pruchnic R et al (2002) Identification of a novel population of muscle stem cells in mice. J Cell Biol 157(5):851–864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren R, Ocampo A, Liu G-H, Izpisua Belmonte JC (2017) Regulation of stem cell aging by metabolism and epigenetics. Cell Metab 26(3):460–474

    Article  CAS  PubMed  Google Scholar 

  • Riazi AM, Kwon SY, Stanford WL (2009) Stem cell sources for regenerative medicine. Methods Mol Biol 482:55–90

    Article  CAS  PubMed  Google Scholar 

  • Sampogna G, Guraya S, Forgione A (2015) Regenerative medicine: historical roots and potential strategies in modern medicine. J Microsc Ultrastruct 3(3):101–107

    Article  PubMed  PubMed Central  Google Scholar 

  • Shafritz D, Oertel M, Menthena A, Nierhoff D, Dabeva M (2006) Liver stem cells and prospects for liver reconstitution by transplanted cells. Hepatology 43(S1):S89–S98

    Article  CAS  PubMed  Google Scholar 

  • Sharpless N, DePinho R (2007) How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol 8(9):703–713

    Article  CAS  PubMed  Google Scholar 

  • Siepe M, Heilmann C, von Samson P, Menasché P, Beyersdorf F (2005) Stem cell research and cell transplantation for myocardial regeneration. Eur J Cardiothorac Surg 28(2):318–324

    Article  PubMed  Google Scholar 

  • Singla D, Hacker T, Ma L, Douglas P, Sullivan R, Lyons G et al (2006) Transplantation of embryonic stem cells into the infarcted mouse heart: formation of multiple cell types. J Mol Cell Cardiol 40(1):195–200

    Article  CAS  PubMed  Google Scholar 

  • Small T, Papadopoulos E, Boulad F, Black P, Castro-Malaspina H, Childs B et al (1999) Comparison of immune reconstitution after unrelated and related T-cell–depleted bone marrow transplantation: effect of patient age and donor leukocyte infusions. Blood 93(2):467–480

    Article  CAS  PubMed  Google Scholar 

  • Smolar J, Horst M, Sulser T, Eberli D (2018) Bladder regeneration through stem cell therapy. Expert Opin Biol Ther 18(5):525–544

    Article  PubMed  Google Scholar 

  • Song Z, Ju Z, Rudolph K (2009) Cell intrinsic and extrinsic mechanisms of stem cell aging depend on telomere status. Exp Gerontol 44(1–2):75–82

    Article  CAS  PubMed  Google Scholar 

  • Stocum D, Zupanc G (2008) Stretching the limits: stem cells in regeneration science. Dev Dyn 237(12):3648–3671

    Article  CAS  PubMed  Google Scholar 

  • Stolzing A, Jones E, McGonagle D, Scutt A (2008) Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev 129(3):163–173

    Article  CAS  PubMed  Google Scholar 

  • Strässler E, Aalto-Setälä K, Kiamehr M, Landmesser U, Kränkel N (2018) Age is relative—impact of donor age on induced pluripotent stem cell-derived cell functionality. Front Cardiovasc Med 5:4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sun N, Youle R, Finkel T (2016) The mitochondrial basis of aging. Mol Cell 61(5):654–666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi J (2018) Stem cells and regenerative medicine for neural repair. Curr Opin Biotechnol 52:102–108

    Article  CAS  PubMed  Google Scholar 

  • Takata N, Eiraku M (2017) Stem cells and genome editing: approaches to tissue regeneration and regenerative medicine. J Hum Genet 63(2):165–178

    Article  PubMed  CAS  Google Scholar 

  • Trohatou O, Roubelakis M (2017) Mesenchymal stem/stromal cells in regenerative medicine: past, present, and future. Cell Reprogram 19(4):217–224

    Article  CAS  PubMed  Google Scholar 

  • Tümpel S, Rudolph K (2012) The role of telomere shortening in somatic stem cells and tissue aging: lessons from telomerase model systems. Ann N Y Acad Sci 1266(1):28–39

    Article  PubMed  Google Scholar 

  • Urbanek K, Torella D, Sheikh F, De Angelis A, Nurzynska D, Silvestri F et al (2005) Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci 102(24):8692–8697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vazin T, Freed W (2010) Human embryonic stem cells: derivation, culture, and differentiation: a review. Restor Neurol Neurosci 28(4):589–603

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vesely I (2005) Heart valve tissue engineering. Circ Res 97(8):743–755

    Article  CAS  PubMed  Google Scholar 

  • Vilchez D, Simic M, Dillin A (2014) Proteostasis and aging of stem cells. Trends Cell Biol 24(3):161–170

    Article  CAS  PubMed  Google Scholar 

  • Weiss D (2014) Concise review: current status of stem cells and regenerative medicine in lung biology and diseases. Stem Cells 32(1):16–25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiseman D (2011) Donor cell leukemia: a review. Biol Blood Marrow Transplant 17(6):771–789

    Article  PubMed  Google Scholar 

  • Xiao L, Nasu M (2014) From regenerative dentistry to regenerative medicine: progress, challenges, and potential applications of oral stem cells. Stem Cells Cloning Adv Appl 2014:89

    Article  Google Scholar 

  • Yao B, Huang S, Gao D, Xie J, Liu N, Fu X (2015) Age-associated changes in regenerative capabilities of mesenchymal stem cell: impact on chronic wounds repair. Int Wound J 13(6):1252–1259

    Article  PubMed  PubMed Central  Google Scholar 

  • Yin H, Price F, Rudnicki M (2013) Satellite cells and the muscle stem cell niche. Physiol Rev 93(1):23–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu Y (2018) Application of stem cell technology in antiaging and aging-related diseases. Adv Exp Med Biol 1086:255–265

    Article  CAS  PubMed  Google Scholar 

  • Yu A, Dang W (2017) Regulation of stem cell aging by SIRT1 – linking metabolic signaling to epigenetic modifications. Mol Cell Endocrinol 455:75–82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Ju Z (2010) Telomere, DNA damage, and oxidative stress in stem cell aging. Birth Defects Res C Embryo Today 90(4):297–307

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Menzies KJ, Auwerx J (2018) The role of mitochondria in stem cell fate and aging. Development 145(8):dev143420

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zulewski H, Abraham E, Gerlach M, Daniel P, Moritz W, Muller B et al (2001) Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate Ex Vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 50(3):521–533

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Life science and Biotechnology, Jadavpur University, Kolkata, India

    Debojyoti De & Parimal Karmakar

  2. Department of Microbiology, Maulana Azad College, Kolkata, India

    Debalina Bhattacharya

Authors
  1. Debojyoti De
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Parimal Karmakar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Debalina Bhattacharya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Debalina Bhattacharya .

Editor information

Editors and Affiliations

  1. (emeritus), Ottawa Hospital Research Institute, Ottawa, ON, Canada

    Kursad Turksen

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

De, D., Karmakar, P., Bhattacharya, D. (2020). Stem Cell Aging and Regenerative Medicine. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 12. Advances in Experimental Medicine and Biology(), vol 1326. Springer, Cham. https://doi.org/10.1007/5584_2020_577

Download citation

Publish with us

Policies and ethics

Search

Navigation