Articolo speciale
Curare con le cellule staminali: miti e realtà attraverso i casi
Stem cell therapy: myths and reality
Andrea Biondi, Giovanna D’Amico, Marta Serafini, Ettore Biagi, Giuseppe Gaipa
Clinica Pediatrica e Centro Tettamanti, Università di Milano-Bicocca, Fondazione MBBM, Ospedale San Gerardo, Monza
Novembre 2014 - pagg. 570 -578
Abstract
Stem cells of various origin nowadays represent a fascinating field of scientific investigation
and clinical application. However, at the same time, particularly in the field of regenerative
medicine, they have generated ambiguous situations, where so defined “scientific
investigators” have created and alimented fake hopes in treating severe degenerative
diseases. The scope of the present article is to give the readers a virtuous path by describing
different clinical cases to show the complexity of the clinical use of such cells as
well as the real scientific-based evidences that justify their use in the context of rigorous
GMP (good manufacturing practice) regulations.
Classificazione MeSH
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Bibliografia
1. Korbling M, Estrov Z. Adult stem cells for
tissue repair - a new therapeutic concept? N
Engl J Med 2003;349(6):570-82.
2. European Medicines Agency, 2010-2011.
3. Vats A, Bielby RC, Tolley NS, Nerem R, Polack
JM. Stem Cells. Lancet 2005;365:592-600.
4. Teo AK, Vallier L. Emerging use of stem
cells in regenerative medicine. Biochem J
2010;428(1):11-23.
5. Klimanskaya I, Rosenthal N, Lanza R. Derive
and conquer: sourcing and differentiating
stem cells for therapeutic applications.
Nat Rev Drug Discov 2008;7(2):131-42.
6. Smith A. A glossary for stem-cell biology.
Nature 2006;441:1060.
7. Seydoux G, Braun RE. Pathway to totipotency:
lessons from germ cells. Cell 2006;
127(5):891-904.
8. Serafini M, Verfaillie CM. Pluripotency in
adult stem cells: state of the art. Semin Reprod
Med 2006;24(5):379-88.
9. Morrison SJ, Uchida N, Weissman IL. The
Biology of Hematopoietic Stem Cells. Annu
Rev Cell Dev Biol 1995;11:35-71.
10. Daniels JT, Dart JK, Tuft SJ, Khaw PT.
Corneal stem cells in review. Wound Repair
Regen 2001;9(6):483-94.
11. Watt FM. Stem cell fate and patterning in
mammalian epidermis. Curr Opin Genet Dev
2001;11:410-7.
12. Rodgerson DO, Harris AG. A comparison
of stem cells for therapeutic use. Stem Cell
Rev 2011;7(4):782-96.
13. Marshak D, Gardner RL, Gottlieb D
(Eds). Stem Cell Biology. Cold Spring Harbor
Laboratory Press, 2001.
14. Friedenstein A. Stromal-hematopoietic interrelationships:
Maximov’s ideas and modern
models. Haematol Blood Transfus 1989;
32:159-67.
15. Kale S, Karihaloo A, Clark PR, Kashgarian
M, Krause DS, Cantley LG. Bone marrow
stem cells contribute to repair of the
ischemically injured renal tubule. J Clin Invest
2003;112:42-9.
16. Ianus A, Holz GG, Theise ND, Hussain
MA. In vivo derivation of glucose-competent
pancreatic endocrine cells from bone marrow
without evidence of cell fusion. J Clin Invest
2003;111:843-50.
17. Alvarez-Dolado M, Pardal R, Garcia-Verdugo
JM, et al. Fusion of bone-marrow-derived
cells with Purkinje neurons, cardiomyocytes
and hepatocytes. Nature 2003;
425:968-73.
18. LaBarge MA, Blau HM. Biological progression
from adult bone marrow to mononucleate
muscle stem cell to multinucleate
muscle fiber in response to injury. Cell 2002;
111:589-601.
19. Jackson KA, Majka SM, Wang H, et al.
Regeneration of ischemic cardiac muscle and
vascular endothelium by adult stem cells. J
Clin Invest 2001;107:1395-402.
20. Pittenger MF, Mackay AM, Beck SC, et al.
Multilineage potential of adult human mesenchymal
stem cells. Science 1999;284:143-7.
21. Reyes M, Lund T, Lenvik T, Aguiar D,
Koodie L, Verfaillie CM. Purification and ex
vivo expansion of postnatal human marrow
mesodermal progenitor cells. Blood 2001;
98:2615-25.
22. Yoon YS, Wecker A, Heyd L, et al. Clonally
expanded novel multipotent stem cells
from human bone marrow regenerate myocardium
after myocardial infarction. J Clin Invest
2005;115:326-38.
23. Kögler G, Sensken S, Airey JA, et al. A
new human somatic stem cell from placental
cord blood with intrinsic pluripotent differentiation
potential. J Exp Med 2004;200:123-35.
24. Wilson A, Trumpp A. Bone-marrow haematopoietic-
stem-cell niches. Nat Rev Immunol
2006;6:93-106.
25. Applebaum FR. Hematopoietic-cell transplantation
at 50. N Engl J Med 2007;357:
1472-5.
26. Anasetti C, Logan BR, Lee SJ, et al. Peripheral-
Blood Stem Cells versus Bone Marrow
from Unrelated Donors. N Engl J Med
2012;367:1487-96.
27. Ballen KK, Gluckman E, Broxmeyer HE.
Umbilical cord blood transplantation: the first
25 years and beyond. Blood 2013;122:491-8.
28. Pellegrini G, Ranno R, Stracuzzi G, et al.
The control of epidermal stem cells (holoclones)
in the treatment of massive full-thickness
burns with autologous keratinocytes
cultured on fibrin. Transplantation 1999;68
(6):868-79.
29. Pellegrini G, Traverso CE, Franzi AT, Zingirian
M, Cancedda R, De Luca M. Long-term
restoration of damaged corneal surfaces with
autologous cultivated corneal epithelium.
Lancet 1997;349(9057):990-3.
30. Rama P, Matuska S, Paganoni G, Spinelli
A, De Luca M, Pellegrini G. Limbal stem-cell
MESSAGGI CHIAVE
o La cellula staminale è in grado di autorinnovarsi,
mantenendo contemporaneamente
la capacità di differenziarsi
in tipologie cellulari distinte.
o Le cellule staminali sono oggetto di
sperimentazioni cliniche, con risultati
promettenti in alcuni contesti specifici.
o Il loro utilizzo clinico deve però seguire
alcune tappe necessarie per garantire
al paziente la sicurezza e la
qualità del trattamento stesso.
o Requisito fondamentale è che la loro
produzione avvenga secondo gli standard
delle buone pratiche di fabbricazione
(GMP) in un’officina autorizzata
da AIFA.
o Le terapie cellulari rappresentano
una sfida che si può vincere solo percorrendo
la strada maestra del metodo
scientifico e delle regole che garantiscono
la sicurezza dei pazienti.
570-578 Articolo Spec nov_PRO_aggiornamento_pennesi 13/11/14 13:24 Pagina 577
Articolo speciale
therapy and long-term corneal regeneration.
N Engl J Med 2010;363(2):147-55.
31. Matsa E, Burridge PW, Wu JC. Human
Stem Cells for Modeling Heart Disease and
for Drug Discovery. Sci Transl Med 2014;6
(239):239ps6.
32. Anderson S, Vanderhaeghen P. Cortical
neurogenesis from pluripotent stem cells:
complexity emerging from simplicity. Curr
Opin Neurobiol 2014;27C:151-7.
33. Thomson JA, Itskovitz-Eldor J, Shapiro
SS, et al. Embryonic stem cell lines derived
from human blastocysts. Science 1998;282:
1145-7.
34. Schwartz SD, Hubschman JP, Heilwell G,
et al. Embryonic stem cell trials for macular
degeneration: a preliminary report. Lancet
2012;379(9817):713-20.
35. Takahashi K, Yamanaka S. Induction of
pluripotent stem cells from mouse embryonic
and adult fibroblast cultures by defined
factors. Cell 2006;126(4):663-76.
36. Robinton DA, Daley GQ. The promise of
induced pluripotent stem cells in research
and therapy. Nature 2012;481(7381):295-305.
37. Krupalnik V, Hanna HJ. Stem cells: The
quest for the perfect reprogrammed cell. Nature
2014;511:160-2.
38. Bianco P. Stem cells in tissue engineering.
Nature 2001;414:118-21.
39. Petite H, Viateau V, Bensaïd W, et al. Tissue-
engineered bone regeneration. Nat Biotechnol
2000;18:959-63.
40. Ashok G. Percutaneous bone marrow
grafting for the treatment of tibial non-union.
Int J Care Injured 2005;36:203-6.
41. Olausson M, Patil PB, Kuna VK, et al.
Transplantation of an allogeneic vein bioengineered
with autologous stem cells: a proof-ofconcept
study. Lancet 2012;380(9838):230-7.
42. Elliott MJ, De Coppi P, Speggiorin S, et al.
Stem-cell-based, tissue engineered tracheal
replacement in a child: a 2-year follow-up
study. Lancet 2012;380(9846):994-1000.
43. Bianco P, Cao X, Frenette PS, et al. The
meaning, the sense and the significance: translating
the science of mesenchymal stem cells
into medicine. Nat Med 2013;19(1):35-42.
44. Fibbe WE, Dazzi F, LeBlanc K. MSCs:
science and trials. Nat Med 2013;19(7):812-3.
45. Castro-Malaspina H, Gay RE, Resnik G,
et al. Characterization of human bone marrow
fibroblast colony-forming cells (CFU-F)
and their progeny. Blood 1980;56:289-301.
46. Capelli C, Salvade A, Pedrini O, et al. The
washouts of discarded bone marrow collection
bags and filters are a very abundant
source of hMSCs. Cytotherapy 2009;11(4):
403-13.
47. Lu LL, Liu YJ, Yang SG, et al. Isolation
and characterization of human umbilical cord
mesenchymal stem cells with hematopoiesissupportive
function and other potentials.
Haematologica 2006;91(8):1017-26.
48. Wu KH, Zhou B, Lu SH, et al. In vitro and
in vivo differentiation of human umbilical
cord derived stem cells into endothelial cells.
J Cell Biochem 2007;100:608-16.
49. Wang HS, Hung SC, Peng ST, et al. Mesenchymal
stem cells in the Wharton’s jelly
of the human umbilical cord. Stem Cells
2004;22:1330-7.
50. Kon E, Muraglia A, Corsi A, et al. Autologous
bone marrow stromal cells loaded onto
porous hydroxyapatite ceramic accelerate bone
repair in critical-size defects of sheep long
bones. J Biomed Mater Res 2000;49:328-37.
51. Bruder SP, Fink DJ, Caplan AI. Mesenchymal
stem cells in bone development, bone
repair, and skeletal regeneration therapy.
J Cell Biochem 1994;56:283-94.
52. Introna M, Lucchini G, Dander E, et al.
Treatment of graft versus host disease with
mesenchymal stromal cells: a phase I study
on 40 adult and pediatric patients. Biol Blood
Marrow Transplant 2014;20(3):375-81.
53. Le Blanc K, Frassoni F, Ball L, et al. Mesenchymal
stem cells for treatment of steroid
resistant, severe, acute graft-versus-host disease:
a phase II study. Lancet 2008;371:1579-86.
54. Bianco P, Cattaneo E, De Luca M, Pani L.
Stamina therapies: Let the record stand. Nature
2014;506(7489):434.
Corrispondenza: abiondi.unimib@gmail.com