Format

Send to

Choose Destination
Stem Cells Transl Med. 2016 Dec;5(12):1631-1643. Epub 2016 Jul 28.

Platelet-Derived Growth Factor-BB Protects Mesenchymal Stem Cells (MSCs) Derived From Immune Thrombocytopenia Patients Against Apoptosis and Senescence and Maintains MSC-Mediated Immunosuppression.

Zhang JM1,2,3, Feng FE1, Wang QM1, Zhu XL1, Fu HX1, Xu LP1,2,3, Liu KY1,2,3, Huang XJ4,2,3, Zhang XH4,2,3.

Author information

1
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
2
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, People's Republic of China.
3
Collaborative Innovation Center of Hematology, Peking University, Beijing, People's Republic of China.
4
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China zhangxh100@sina.com xjhrm@medmail.com.cn.

Abstract

: Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Mesenchymal stem cells (MSCs) from ITP patients (MSC-ITP) do not exhibit conventional proliferative abilities and thus exhibit defects in immunoregulation, suggesting that MSC impairment might be a mechanism involved in ITP. Platelet-derived growth factor (PDGF) improves growth and survival in various cell types. Moreover, PDGF promotes MSC proliferation. The aim of the present study was to analyze the effects of PDGF-BB on MSC-ITP. We showed that MSC-ITP expanded more slowly and appeared flattened and larger. MSC-ITP exhibited increased apoptosis and senescence compared with controls. Both the intrinsic and extrinsic pathways account for the enhanced apoptosis. P53 and p21 expression were upregulated in MSC-ITP, but inhibition of p53 with pifithrin-α markedly inhibited apoptosis and senescence. Furthermore, MSCs from ITP patients showed a lower capacity for inhibiting the proliferation of activated T cells inducing regulatory T cells (Tregs) and suppressing the synthesis of anti-glycoprotein (GP)IIb-IIIa antibodies. PDGF-BB treatment significantly decreased the expression of p53 and p21 and increased survivin expression in MSC-ITP. In addition, the apoptotic rate and number of senescent cells in ITP MSCs were reduced. Their impaired ability for inhibiting activated T cells, inducing Tregs, and suppressing the synthesis of anti-GPIIb-IIIa antibodies was restored after PDGF-BB treatment. In conclusion, we have demonstrated that PDGF-BB protects MSCs derived from ITP patients against apoptosis, senescence, and immunomodulatory defects. This protective effect of PDGF-BB is likely mediated via the p53/p21 pathway, thus potentially providing a new therapeutic approach for ITP.

SIGNIFICANCE:

Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Platelet-derived growth factor (PDGF) improves growth and survival in various cell types and promotes mesenchymal stem cell (MSC) proliferation. PDGF-BB protects MSCs derived from ITP patients against apoptosis, senescence, and immunomodulatory defects. This protective effect of PDGF-BB is likely mediated via the p53/p21 pathway, thus potentially providing a new therapeutic approach for ITP.

KEYWORDS:

Apoptosis; Immunosuppression; Mesenchymal stem cells; Platelet-derived growth factor-BB; Senescence

PMID:
27471307
PMCID:
PMC5189646
DOI:
10.5966/sctm.2015-0360
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center