Adipose tissue‑derived stem cells modulate immune function in vivo and promote long‑term hematopoiesis in vitro using the aGVHD model

Jiang,Ming; Bi,Xiaojuan; Duan,Xianlin; Pang,Nannan; Wang,Hongbo; Yuan,Hailong; Zhang,Rongyao; Cui,Lei

doi:10.3892/etm.2020.8430

Adipose tissue‑derived stem cells modulate immune function in vivo and promote long‑term hematopoiesis in vitro using the aGVHD model

Authors:
- Ming Jiang
- Xiaojuan Bi
- Xianlin Duan
- Nannan Pang
- Hongbo Wang
- Hailong Yuan
- Rongyao Zhang
- Lei Cui
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Affiliations: Hematologic Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region Research Institute of Hematology, Urumqi, Xinjiang Uygur Autonomous Region 830054, P.R. China, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830054, P.R. China
Published online on: January 7, 2020 https://doi.org/10.3892/etm.2020.8430
Pages: 1725-1732
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study was designed to investigate the effect of adipose‑derived stem cells (ADSCs) on acute graft vs. host disease (aGVHD) and hematopoietic recovery after allogeneic hematopoietic stem cell transplantation. ADSCs, bone marrow‑derived stem cells (BMSCs) and fibroblasts were cultured. ADSCs were cocultured with hematopoietic stem/progenitor cells. Then, ADSCs were infused into the aGVHD rat model. The survival of the rats was recorded. Livers and small intestines were obtained from sacrificed rats for pathological examinations. Expression of the Sry gene in recipient rats that survived longer than 21 days was examined by real‑time PCR to detect the presence of donor Y chromosome. Expression of serum interferon (INF)‑γ and interleukin (IL)‑4 was detected by ELISA at 0, 7, 14, 21 and 50 days after transplantation. Transplantation of ADSCs improved the survival of aGVHD rats. Survived ADSCs participated in hematopoietic reconstitution in aGVHD rats. ADSCs decreased aGVHD severity by immunomodulation. ADSCs support the proliferation of hematopoietic stem/progenitor cells in vitro. The present study demonstrated that ADSCs may reduce aGVHD by influencing the balance of IL‑4 and INF‑γ and can promote long‑term hematopoiesis.

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1	Piemontese S, Ciceri F, Labopin M, Bacigalupo A, Huang H, Santarone S, Gorin NC, Koc Y, Wu D, Beelen D, et al: A survey on unmanipulated haploidentical hematopoietic stem cell transplantation in adults with acute leukemia. Leukemia. 29:1069–1075. 2015. View Article : Google Scholar : PubMed/NCBI
2	Murray IR, West CC, Hardy WR, James AW, Park TS, Nguyen A, Tawonsawatruk T, Lazzari L, Soo C and Péault B: Natural history of mesenchymal stem cells, from vessel walls to culture vessels. Cell Mol Life Sci. 71:1353–1374. 2014. View Article : Google Scholar : PubMed/NCBI
3	Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M and Ringdén O: Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 363:1439–1441. 2004. View Article : Google Scholar : PubMed/NCBI
4	Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP and Hedrick MH: Multilineage cells from human adipose tissue: Implications for cell-based therapies. Tissue Eng. 7:211–228. 2001. View Article : Google Scholar : PubMed/NCBI
5	Mirlashari MJ, Josefsen D, Landsverk K, Hasvold G, Gullestad H and Kvalheim G: Culturing of human adipose derived mesenchymal stem cells (ADSCS) under hypoxic conditions affects production of wound healing cytokines and growth factors. Cytotherapy. 16:S932014. View Article : Google Scholar
6	Institute of Laboratory Animal Resources (US). Committee on Care and Use of Laboratory Animals. Guide for the care and use of laboratory animals. US Department of Health and Human Services, Public Health Service, National Institutes of Health. 1986.
7	Frazier K, Williams S, Kothapalli D, Klapper H and Grotendorst GR: Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor. J Invest Dermatol. 107:404–411. 1996. View Article : Google Scholar : PubMed/NCBI
8	Hu J, Yan M, Jiang M, Shi W, Xu Y, Zhang D and Li J: Establishment of a rat model of acute graft-versus-host disease after allogeneic bone marrow transplantation. Chin J Com Med. 17:581–584. 2007.
9	Vogelsang GB, Hess AD, Gordon G and Santos GW: Treatment and prevention of acute graft-versus-host disease with thalidomide in a rat model. Transplantation. 41:644–647. 1986. View Article : Google Scholar : PubMed/NCBI
10	Renkonen R and Häyry P: Bone marrow transplantation in the rat. I. Histologic correlations and quantitation of cellular infiltrates in acute graft-versus-host disease. Am J Pathol. 117:462–470. 1984.PubMed/NCBI
11	Ju XP, Xu B, Xiao ZP, Li JY, Chen L, Lu SQ and Huang ZX: Cytokine expression during acute graft-versus-host disease after allogeneic peripheral stem cell transplantation. Bone Marrow Transplant. 35:1179–1186. 2005. View Article : Google Scholar : PubMed/NCBI
12	Dong Y, Zhu T, Xia R, Li Y, Ge X, Zeng Q, Ni J and Li Q: Mechanism of bone marrow mesenchymal stem cells for treating model mice with aplastic anemia. J Clin Rehabil Tissue Eng Res. 13:7138–7142. 2009.
13	Wu KH, Tsai C, Wu HP, Sieber M, Peng CT and Chao YH: Human application of ex vivo expanded umbilical cord-derived mesenchymal stem cells: Enhance hematopoiesis after cord blood transplantation. Cell Transplant. 22:2041–2051. 2013. View Article : Google Scholar : PubMed/NCBI
14	Kern S, Eichler H, Stoeve J, Klüter H and Bieback K: Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 24:1294–1301. 2006. View Article : Google Scholar : PubMed/NCBI
15	Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, et al: Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: A phase II study. Lancet. 371:1579–1586. 2008. View Article : Google Scholar : PubMed/NCBI
16	Te Boome LC, Mansilla C, van der Wagen LE, Lindemans CA, Petersen EJ, Spierings E, Thus KA, Westinga K, Plantinga M, Bierings M, et al: Biomarker profiling of steroid-resistant acute GVHD in patients after infusion of mesenchymal stromal cells. Leukemia. 29:1839–1846. 2015. View Article : Google Scholar : PubMed/NCBI
17	Jitschin R, Mougiakakos D, Von Bahr L, Völkl S, Moll G, Ringden O, Kiessling R, Linder S and Le Blanc K: Alterations in the cellular immune compartment of patients treated with third-party mesenchymal stromal cells following allogeneic hematopoietic stem cell transplantation. Stem Cells. 31:1715–1725. 2013. View Article : Google Scholar : PubMed/NCBI
18	Galipeau J: The mesenchymal stromal cells dilemma-does a negative phase III trial of random donor mesenchymal stromal cells in steroid-resistant graft-versus-host disease represent a death knell or a bump in the road? Cytotherapy. 15:2–8. 2013. View Article : Google Scholar : PubMed/NCBI
19	Bora P and Majumdar AS: Adipose tissue-derived stromal vascular fraction in regenerative medicine: A brief review on biology and translation. Stem Cell Res Ther. 8:1452017. View Article : Google Scholar : PubMed/NCBI
20	Schäffler A and Büchler C: Concise review: Adipose tissue-derived stromal cells-basic and clinical implications for novel cell-based therapies. Stem Cells. 25:818–827. 2007. View Article : Google Scholar : PubMed/NCBI
21	Zhang Y, Zhu Y, Li Y, Cao J, Zhang H, Chen M, Wang L and Zhang C: Long-term engraftment of myogenic progenitors from adipose-derived stem cells and muscle regeneration in dystrophic mice. Hum Mol Genet. 24:6029–6040. 2015. View Article : Google Scholar : PubMed/NCBI
22	Bai W, Jiang M, Cui L and Yi S: An experimental study for the immunological properties of human adipose-derived stem cells after expansion. J Tissue Eng Reconstr Sur. 4:312–314. 2008.
23	Cui L, Yin S, Liu W, Li N, Zhang W and Cao Y: Expanded adipose-derived stem cells suppress mixed lymphocyte reaction by secretion of prostaglandin E2. Tissue Eng. 13:1185–1195. 2007. View Article : Google Scholar : PubMed/NCBI
24	Yañez R, Lamana ML, García-Castro J, Colmenero I, Ramírez M and Bueren JA: Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem Cells. 24:2582–2591. 2006. View Article : Google Scholar : PubMed/NCBI
25	Yao Y, Song X, Cheng H, Tang G, Hu X, Zhou H and Wang J: Dysfunction of bone marrow vascular niche in acute graft-versus-host disease after MHC-haploidentical bone marrow transplantation. PLoS One. 9:e1046072014. View Article : Google Scholar : PubMed/NCBI
26	Nasef A, Chapel A, Mazurier C, Bouchet S, Lopez M, Mathieu N, Sensebé L, Zhang Y, Gorin NC, Thierry D and Fouillard L: Identification of IL-10 and TGF-beta transcripts involved in the inhibition of T-lymphocyte proliferation during cell contact with human mesenchymal stem cells. Gene Expr. 13:217–226. 2007. View Article : Google Scholar : PubMed/NCBI
27	Najar M, Rouas R, Raicevic G, Boufker HI, Lewalle P, Meuleman N, Bron D, Toungouz M, Martiat P and Lagneaux L: Mesenchymal stromal cells promote or suppress the proliferation of T lymphocytes from cord blood and peripheral blood: The importance of low cell ratio and role of interleukin-6. Cytotherapy. 11:570–583. 2009. View Article : Google Scholar : PubMed/NCBI
28	de Barros AP, Takiya CM, Garzoni LR, Leal-Ferreira ML, Dutra HS, Chiarini LB, Meirelles MN, Borojevic R and Rossi MI: Osteoblasts and bone marrow mesenchymal stromal cells control hematopoietic stem cell migration and proliferation in 3D in vitro model. PLoS One. 5:e90932010. View Article : Google Scholar : PubMed/NCBI
29	Arthur A, Cakouros D, Cooper L, Nguyen T, Isenmann S, Zannettino AC, Glackin CA and Gronthos S: Twist-1 enhances bone marrow mesenchymal stromal cell support of hematopoiesis by modulating CXCL12 expression. Stem Cells. 34:504–509. 2016. View Article : Google Scholar : PubMed/NCBI
30	Sun HP, Zhang X, Chen XH, Zhang C and Gao L, Feng YM, Peng XG and Gao L: Human umbilical cord blood-derived stromal cells are superior to human umbilical cord blood-derived mesenchymal stem cells in inducing myeloid lineage differentiation in vitro. Stem Cells Dev. 21:1429–1440. 2012. View Article : Google Scholar : PubMed/NCBI
31	Zhang R, Bi X, Ma Y, Duan X and Jiang M: Biological characterization of C57 mouse bone marrow mesenchymal stem cells using a whole bone marrow adherent culture technique. Chin J Tissue Eng Res. 18:45–50. 2014.