Multipotent Mesenchymal Stromal Cell Therapy and Risk of Malignancies

被引:128
作者
Casiraghi, Federica [1 ,2 ]
Remuzzi, Giuseppe [1 ]
Abbate, Mauro [1 ]
Perico, Norberto [1 ]
机构
[1] Ospedali Riuniti, Mario Negri Inst Pharmacol Res, Dept Immunol & Transplantat, Transplant Res Ctr Chiara Cucchi de Alessandri &, Bergamo, Italy
[2] Mario Negri Inst Pharmacol Res, Transplant Res Ctr Chiara Cucchi de Alessandri &, I-24020 Bergamo, Italy
关键词
Multipotent mesenchymal stromal cells; Malignant maldifferentiation; Cancer; Tumor; Safety; VERSUS-HOST-DISEASE; HEMATOPOIETIC STEM-CELLS; AMYOTROPHIC-LATERAL-SCLEROSIS; BREAST-CANCER GROWTH; BONE-MARROW; IN-VITRO; TUMOR-GROWTH; CROSS-CONTAMINATION; PROGENITOR CELLS; DOWN-REGULATION;
D O I
10.1007/s12015-011-9345-4
中图分类号
Q813 [细胞工程];
学科分类号
100113 [医学细胞生物学];
摘要
Cell therapy with Multipotent Mesenchymal Stromal Cells (MSC) holds enormous promise for the treatment of a large number of degenerative and immune/inflammatory diseases. Their multilineage differentiation potential, immunoprivilege and capacity of promoting recovery of damaged tissues coupled with anti-inflammatory and immunosuppressive properties are the focus of a multitude of clinical studies currently underway. The recognized clinical potential of MSC repairing/immunomodulatory effects now encompasses graft-versus-host disease, hematologic malignancies, cardiovascular diseases, neurologic and inherited diseases, autoimmune diseases, organ transplantation, refractory wounds, and bone/cartilage defects among others. However, it has been suggested that both the need of extensive ex vivo culture for MSC clinical use, and their proangiogenic, anti-apoptotic and immunomodulatory properties may act together as tumor promoters, raising significant safety concerns. This paper will review the available data on in vitro MSC maldifferentiation and the ability of MSC to sustain tumor growth in vivo, with the aim to clarify whether MSC-based therapeutic approaches may carry actual risk of malignancies.
引用
收藏
页码:65 / 79
页数:15
相关论文
共 139 条
[1]
Murine but not human mesenchymal stem cells generate osteosarcoma-like lesions in the lung [J].
Aguilar, Susana ;
Nye, Emma ;
Chan, Jerry ;
Loebinger, Michael ;
Spencer-Dene, Bradley ;
Fisk, Nick ;
Stamp, Gordon ;
Bonnet, Dominique ;
Janes, Sam M. .
STEM CELLS, 2007, 25 (06) :1586-1594
[2]
Dynamic of distribution of human bone marrow-derived mesenchymal stem cells after transplantation into adult unconditioned mice [J].
Allers, C ;
Sierralta, WD ;
Neubauer, S ;
Rivera, F ;
Minguell, JJ ;
Conget, PA .
TRANSPLANTATION, 2004, 78 (04) :503-508
[3]
Hypoxia promotes murine bone-marrow-derived stromal cell migration and tube formation [J].
Annabi, B ;
Lee, YT ;
Turcotte, S ;
Naud, E ;
Desrosiers, RR ;
Champagne, M ;
Eliopoulos, N ;
Galipeau, J ;
Béliveau, R .
STEM CELLS, 2003, 21 (03) :337-347
[4]
Vascular progenitors derived from murine bone marrow stromal cells are regulated by fibroblast growth factor and are avidly recruited by vascularizing tumors [J].
Annabi, B ;
Naud, E ;
Lee, YT ;
Eliopoulos, N ;
Galipeau, J .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2004, 91 (06) :1146-1158
[5]
Single intra-arterial injection of mesenchymal stromal cells for treatment of steroid-refractory acute graft-versus-host disease: a pilot study [J].
Arima, Nobuyoshi ;
Nakamura, Fumiaki ;
Fukunaga, Akiko ;
Hirata, Hirokazu ;
Machida, Hiroko ;
Kouno, Shigene ;
Ohgushi, Hajime .
CYTOTHERAPY, 2010, 12 (02) :265-268
[6]
p53 regulates the proliferation, differentiation and spontaneous transformation of mesenchymal stem cells [J].
Armesilla-Diaz, Alejandro ;
Elvira, Gema ;
Silva, Augusto .
EXPERIMENTAL CELL RESEARCH, 2009, 315 (20) :3598-3610
[7]
Cotransplantation of ex vivo-expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation [J].
Ball, Lynne M. ;
Bernardo, Maria Ester ;
Roelofs, Helene ;
Lankester, Arjan ;
Cometa, Angela ;
Egeler, R. Maarten ;
Locatelli, Franco ;
Fibbe, Willem E. .
BLOOD, 2007, 110 (07) :2764-2767
[8]
Autologous mesenchymal stem cell transplantation in stroke patients [J].
Bang, OY ;
Lee, JS ;
Lee, PH ;
Lee, G .
ANNALS OF NEUROLOGY, 2005, 57 (06) :874-882
[9]
VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma [J].
Beckermann, B. M. ;
Kallifatidis, G. ;
Groth, A. ;
Frommhold, D. ;
Apel, A. ;
Mattern, J. ;
Salnikov, A. V. ;
Moldenhauer, G. ;
Wagner, W. ;
Diehlmann, A. ;
Saffrich, R. ;
Schubert, M. ;
Ho, A. D. ;
Giese, N. ;
Buechler, M. W. ;
Friess, H. ;
Buechler, P. ;
Herr, I. .
BRITISH JOURNAL OF CANCER, 2008, 99 (04) :622-631
[10]
Human bone marrow-derived mesenchymal stem cells do not undergo transformation after long-term In vitro culture and do not exhibit telomere maintenance mechanisms [J].
Bernardo, Maria Ester ;
Zaffaroni, Nadia ;
Novara, Francesca ;
Cometa, Angela Maria ;
Avanzini, Maria Antonietta ;
Moretta, Antonia ;
Montagna, Daniela ;
Maccario, Rita ;
Villa, Raffaella ;
Daidone, Maria Grazia ;
Zuffardi, Orsetta ;
Locatelli, Franco .
CANCER RESEARCH, 2007, 67 (19) :9142-9149