Effects of human umbilical cord-derived mesenchymal stem cells on hematologic malignancies

Li,Qian; Pang,Yilin; Liu,Tingting; Tang,Yongyong; Xie,Jing; Zhang,Bin; Chen,Hu

doi:10.3892/ol.2018.8254

Effects of human umbilical cord-derived mesenchymal stem cells on hematologic malignancies

Authors:
- Qian Li
- Yilin Pang
- Tingting Liu
- Yongyong Tang
- Jing Xie
- Bin Zhang
- Hu Chen
View Affiliations

Affiliations: Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, P.R. China
Published online on: March 13, 2018 https://doi.org/10.3892/ol.2018.8254
Pages: 6982-6990
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Mesenchymal stem cells (MSCs) have been used in hematopoietic stem cell transplantation for years. However, the safety of MSCs applied in various types of hematologic malignancy has not been comprehensively explored. In the present study, the effects of human umbilical cord‑derived mesenchymal stem cells (hUC‑MSCs) on six representative hematologic malignancy cell lines were explored, including leukemia, multiple myeloma and lymphoma cells. Direct and indirect co‑culture models were established, and cell proliferation was assessed by carboxyfluorescein diacetate succinimidyl ester staining. A cytometric bead array cytokine kit was used to quantify cytokines. The expression of interleukin (IL)-6 receptor elements on tumor cells was detected by reverse transcription‑polymerase chain reaction and flow cytometry, and the effects of exogenous IL‑6 on cell proliferation were determined using a Cell Counting kit‑8 assay. The results demonstrated that hUC‑MSCs inhibited the proliferation of most of the cell lines examined (THP‑1, HL‑60, K562 and RPMI‑8226), but promoted the proliferation of Raji cells. In addition, hUC‑MSCs secreted abundant IL‑6, promoted the secretion of IL‑10 by RPMI‑8226 and Raji cells, and inhibited the secretion of tumor necrosis factor‑α by THP‑1 cells. These data indicate a varied effect of hUC‑MSCs on various types of hematologic malignancy, including distinct mechanisms of cell‑to‑cell contact and cytokines. Researchers applying hUC‑MSCs in lymphoma should be aware of a potential tumor growth-promoting effect.

View Figures

View References

1	Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S and Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science. 284:143–147. 1999. View Article : Google Scholar : PubMed/NCBI
2	El Omar R, Beroud J, Stoltz JF, Menu P, Velot E and Decot V: Umbilical cord mesenchymal stem cells: The new gold standard for mesenchymal stem cell-based therapies? Tissue Eng Part B Rev. 20:523–544. 2014. View Article : Google Scholar : PubMed/NCBI
3	Nuschke A: Activity of mesenchymal stem cells in therapies for chronic skin wound healing. Organogenesis. 10:29–37. 2014. View Article : Google Scholar : PubMed/NCBI
4	Ra JC, Kang SK, Shin IS, Park HG, Joo SA, Kim JG, Kang BC, Lee YS, Nakama K, Piao M, et al: Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells. J Transl Med. 9:1812011.PubMed/NCBI
5	Bhansali A, Asokumar P, Walia R, Bhansali S, Gupta V, Jain A, Sachdeva N, Sharma RR, Marwaha N and Khandelwal N: Efficacy and safety of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus: A randomized placebo-controlled study. Cell Transplant. 23:1075–1085. 2014. View Article : Google Scholar : PubMed/NCBI
6	Knaän-Shanzer S: Concise review: The immune status of mesenchymal stem cells and its relevance for therapeutic application. Stem Cells. 32:603–608. 2014. View Article : Google Scholar : PubMed/NCBI
7	Castro-Manrreza ME and Montesinos JJ: Immunoregulation by mesenchymal stem cells: Biological aspects and clinical applications. J Immunol Res. 2015:3949172015. View Article : Google Scholar : PubMed/NCBI
8	Vaes B, Van't Hof W, Deans R and Pinxteren J: Application of MultiStem(®) allogeneic cells for immunomodulatory therapy: Clinical progress and Pre-clinical challenges in prophylaxis for graft versus host disease. Front Immunol. 3:3452012. View Article : Google Scholar : PubMed/NCBI
9	Zhang L, Xiang J and Li G: The uncertain role of unmodified mesenchymal stem cells in tumor progression: What master switch? Stem Cell Res Ther. 4:222013. View Article : Google Scholar : PubMed/NCBI
10	Hong IS, Lee HY and Kang KS: Mesenchymal stem cells and cancer: Friends or enemies? Mutat Res. 768:98–106. 2014. View Article : Google Scholar : PubMed/NCBI
11	Yang X, Hou J, Han Z, Wang Y, Hao C, Wei L and Shi Y: One cell, multiple roles: Contribution of mesenchymal stem cells to tumor development in tumor microenvironment. Cell Biosci. 3:52013. View Article : Google Scholar : PubMed/NCBI
12	Ning H, Yang F, Jiang M, Hu L, Feng K, Zhang J, Yu Z, Li B, Xu C, Li Y, et al: The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: Outcome of a pilot clinical study. Leukemia. 22:593–599. 2008. View Article : Google Scholar : PubMed/NCBI
13	Nomoto-Kojima N, Aoki S, Uchihashi K, Matsunobu A, Koike E, Ootani A, Yonemitsu N, Fujimoto K and Toda S: Interaction between adipose tissue stromal cells and gastric cancer cells in vitro. Cell Tissue Res. 344:287–298. 2011. View Article : Google Scholar : PubMed/NCBI
14	Seo SH, Kim KS, Park SH, Suh YS, Kim SJ, Jeun SS and Sung YC: The effects of mesenchymal stem cells injected via different routes on modified IL-12-mediated antitumor activity. Gene Ther. 18:488–495. 2011. View Article : Google Scholar : PubMed/NCBI
15	Sarmadi VH, Tong CK, Vidyadaran S, Abdullah M, Seow HF and Ramasamy R: Mesenchymal stem cells inhibit proliferation of lymphoid origin haematopoietic tumour cells by inducing cell cycle arrest. Med J Malaysia. 65:209–214. 2010.PubMed/NCBI
16	Carrade DD, Lame MW, Kent MS, Clark KC, Walker NJ and Borjesson DL: Comparative analysis of the immunomodulatory properties of equine Adult-derived mesenchymal stem cells(). Cell Med. 4:1–11. 2012. View Article : Google Scholar : PubMed/NCBI
17	Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC and Shi Y: Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2:141–150. 2008. View Article : Google Scholar : PubMed/NCBI
18	Hu J, Yang Z, Wang J, Tang Y, Liu H, Zhang B and Chen H: Infusion of Trx-1-overexpressing hucMSC prolongs the survival of acutely irradiated NOD/SCID mice by decreasing excessive inflammatory injury. PLoS One. 8:e782272013. View Article : Google Scholar : PubMed/NCBI
19	Jones SA, Scheller J and Rose-John S: Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. J Clin Invest. 121:3375–3383. 2011. View Article : Google Scholar : PubMed/NCBI
20	Batsali AK, Kastrinaki MC, Papadaki HA and Pontikoglou C: Mesenchymal stem cells derived from Wharton's Jelly of the umbilical cord: Biological properties and emerging clinical applications. Curr Stem Cell Res Ther. 8:144–155. 2013. View Article : Google Scholar : PubMed/NCBI
21	Ramasamy R, Lam EW, Soeiro I, Tisato V, Bonnet D and Dazzi F: Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: Impact on in vivo tumor growth. Leukemia. 21:304–310. 2007. View Article : Google Scholar : PubMed/NCBI
22	Fonseka M, Ramasamy R, Tan BC and Seow HF: Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) inhibit the proliferation of K562 (human erythromyeloblastoid leukaemic cell line). Cell Biol Int. 36:793–801. 2012. View Article : Google Scholar : PubMed/NCBI
23	Cetintas Bozok V, Aktug H, Oltulu F, Keskinoglu A, Del Castello Erer B and Taskiran D: The effects of mesenchymal stem cells on lymphoblastic leukemia cell proliferation. J BUON. 19:1006–1017. 2014.PubMed/NCBI
24	Zhu Y, Sun Z, Han Q, Liao L, Wang J, Bian C, Li J, Yan X, Liu Y, Shao C and Zhao RC: Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukemia. 23:925–933. 2009. View Article : Google Scholar : PubMed/NCBI
25	Rosean TR, Tompkins VS, Tricot G, Holman CJ, Olivier AK, Zhan F and Janz S: Preclinical validation of interleukin 6 as a therapeutic target in multiple myeloma. Immunol Res. 59:188–202. 2014. View Article : Google Scholar : PubMed/NCBI
26	Klein B, Tarte K, Jourdan M, Mathouk K, Moreaux J, Jourdan E, Legouffe E, De Vos J and Rossi JF: Survival and proliferation factors of normal and malignant plasma cells. Int J Hematol. 78:106–113. 2003. View Article : Google Scholar : PubMed/NCBI
27	Voorhees PM, Manges RF, Sonneveld P, Jagannath S, Somlo G, Krishnan A, Lentzsch S, Frank RC, Zweegman S, Wijermans PW, et al: A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma. Br J Haematol. 161:357–366. 2013. View Article : Google Scholar : PubMed/NCBI
28	Matsuyama Y, Nagashima T, Honne K, Kamata Y, Iwamoto M, Okazaki H, Sato K, Ozawa K and Minota S: Successful treatment of a patient with rheumatoid arthritis and IgA-k multiple myeloma with tocilizumab. Intern Med. 50:639–642. 2011. View Article : Google Scholar : PubMed/NCBI
29	Ahn JO, Chae JS, Coh YR, Jung WS, Lee HW, Shin IS, Kang SK and Youn HY: Human adipose tissue-derived mesenchymal stem cells inhibit T-cell lymphoma growth in vitro and in vivo. Anticancer Res. 34:4839–4847. 2014.PubMed/NCBI
30	Medina DJ, Goodell L, Glod J, Gelinas C, Rabson AB and Strair RK: Mesenchymal stromal cells protect mantle cell lymphoma cells from spontaneous and drug-induced apoptosis through secretion of B-cell activating factor and activation of the canonical and non-canonical nuclear factor kB pathways. Haematologica. 97:1255–1263. 2012. View Article : Google Scholar : PubMed/NCBI
31	Guney N, Soydinc HO, Basaran M, Bavbek S, Derin D, Camlica H, Yasasever V and Topuz E: Serum levels of interleukin-6 and interleukin-10 in Turkish patients with aggressive non-Hodgkin's lymphoma. Asian Pac J Cancer Prev. 10:669–674. 2009.PubMed/NCBI
32	Kovacs E: Interleukin-6 leads to interleukin-10 production in several human multiple myeloma cell lines. Does interleukin-10 enhance the proliferation of these cells? Leuk Res. 34:912–916. 2010. View Article : Google Scholar : PubMed/NCBI