Encapsulated Therapeutic Stem Cells Implanted in the Tumor Resection Cavity Induce Cell Death in Gliomas

Overview

Journal Nat Neurosci

Date 2011 Dec 27

PMID 22197831

Citations 108

Authors

Timo M Kauer

Jose-Luiz Figueiredo

Shawn Hingtgen

Khalid Shah

Affiliations

Soon will be listed here.

Abstract

Therapeutically engineered stem cells have shown promise for glioblastoma multiforme (GBM) therapy; however, key preclinical studies are urgently needed for their clinical translation. In this study, we investigated a new approach to GBM treatment using therapeutic stem cells encapsulated in biodegradable, synthetic extracellular matrix (sECM) in mouse models of human GBM resection. Using multimodal imaging, we first showed quantitative surgical debulking of human GBM tumors in mice, which resulted in increased survival. Next, sECM encapsulation of engineered stem cells increased their retention in the tumor resection cavity, permitted tumor-selective migration and release of diagnostic and therapeutic proteins in vivo. Simulating the clinical scenario of GBM treatment, the release of tumor-selective S-TRAIL (secretable tumor necrosis factor apoptosis inducing ligand) from sECM-encapsulated stem cells in the resection cavity eradicated residual tumor cells by inducing caspase-mediated apoptosis, delayed tumor regrowth and significantly increased survival of mice. This study demonstrates the efficacy of encapsulated therapeutic stem cells in mouse models of GBM resection and may have implications for developing effective therapies for GBM.

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References

Ma W, Fitzgerald W, Liu Q, OShaughnessy T, Maric D, Lin H . CNS stem and progenitor cell differentiation into functional neuronal circuits in three-dimensional collagen gels. Exp Neurol. 2004; 190(2):276-88. DOI: 10.1016/j.expneurol.2003.10.016. View

Teng Y, Lavik E, Qu X, Park K, Ourednik J, Zurakowski D . Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc Natl Acad Sci U S A. 2002; 99(5):3024-9. PMC: 122466. DOI: 10.1073/pnas.052678899. View

Corsten M, Shah K . Therapeutic stem-cells for cancer treatment: hopes and hurdles in tactical warfare. Lancet Oncol. 2008; 9(4):376-84. DOI: 10.1016/S1470-2045(08)70099-8. View

Menon L, Kelly K, Yang H, Kim S, Black P, Carroll R . Human bone marrow-derived mesenchymal stromal cells expressing S-TRAIL as a cellular delivery vehicle for human glioma therapy. Stem Cells. 2009; 27(9):2320-30. DOI: 10.1002/stem.136. View

Kim S, Oh J, Park S, Ryu C, Lim J, Kim D . Irradiation enhances the tumor tropism and therapeutic potential of tumor necrosis factor-related apoptosis-inducing ligand-secreting human umbilical cord blood-derived mesenchymal stem cells in glioma therapy. Stem Cells. 2010; 28(12):2217-28. DOI: 10.1002/stem.543. View

Karnoub A, Dash A, Vo A, Sullivan A, Brooks M, Bell G . Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007; 449(7162):557-63. DOI: 10.1038/nature06188. View

Shah K . Mesenchymal stem cells engineered for cancer therapy. Adv Drug Deliv Rev. 2011; 64(8):739-48. PMC: 3395998. DOI: 10.1016/j.addr.2011.06.010. View

De Oliveira M, Cechim G, Braganhol E, Santos D, Meurer L, de Castro Jr C . Anti-proliferative effect of the gastrin-release peptide receptor antagonist RC-3095 plus temozolomide in experimental glioblastoma models. J Neurooncol. 2009; 93(2):191-201. DOI: 10.1007/s11060-008-9775-2. View

Snyder E . The risk of putting something where it does not belong: mesenchymal stem cells produce masses in the brain. Exp Neurol. 2011; 230(1):75-7. DOI: 10.1016/j.expneurol.2011.03.012. View

10.

Sasportas L, Kasmieh R, Wakimoto H, Hingtgen S, van de Water J, Mohapatra G . Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci U S A. 2009; 106(12):4822-7. PMC: 2660771. DOI: 10.1073/pnas.0806647106. View

11.

Hall B, Dembinski J, Sasser A, Studeny M, Andreeff M, Marini F . Mesenchymal stem cells in cancer: tumor-associated fibroblasts and cell-based delivery vehicles. Int J Hematol. 2007; 86(1):8-16. DOI: 10.1532/IJH97.06230. View

12.

Choi S, Lee J, Wang K, Phi J, Song S, Song J . Human adipose tissue-derived mesenchymal stem cells: characteristics and therapeutic potential as cellular vehicles for prodrug gene therapy against brainstem gliomas. Eur J Cancer. 2011; 48(1):129-37. DOI: 10.1016/j.ejca.2011.04.033. View

13.

Tian X, Ye J, Alonso-Basanta M, Hahn S, Koumenis C, Dorsey J . Modulation of CCAAT/enhancer binding protein homologous protein (CHOP)-dependent DR5 expression by nelfinavir sensitizes glioblastoma multiforme cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). J Biol Chem. 2011; 286(33):29408-29416. PMC: 3190746. DOI: 10.1074/jbc.M110.197665. View

14.

Affronti M, Heery C, Herndon 2nd J, Rich J, Reardon D, Desjardins A . Overall survival of newly diagnosed glioblastoma patients receiving carmustine wafers followed by radiation and concurrent temozolomide plus rotational multiagent chemotherapy. Cancer. 2009; 115(15):3501-11. DOI: 10.1002/cncr.24398. View

15.

Pan L, Ren Y, Cui F, Xu Q . Viability and differentiation of neural precursors on hyaluronic acid hydrogel scaffold. J Neurosci Res. 2009; 87(14):3207-20. DOI: 10.1002/jnr.22142. View

16.

Adamson C, Kanu O, Mehta A, Di C, Lin N, Mattox A . Glioblastoma multiforme: a review of where we have been and where we are going. Expert Opin Investig Drugs. 2009; 18(8):1061-83. DOI: 10.1517/13543780903052764. View

17.

Siegelin M, Gaiser T, Habel A, Siegelin Y . Daidzein overcomes TRAIL-resistance in malignant glioma cells by modulating the expression of the intrinsic apoptotic inhibitor, bcl-2. Neurosci Lett. 2009; 454(3):223-8. DOI: 10.1016/j.neulet.2009.03.031. View

18.

Chen J, Sun X, Yang W, Jiang G, Li X . Cisplatin-enhanced sensitivity of glioblastoma multiforme U251 cells to adenovirus-delivered TRAIL in vitro. Tumour Biol. 2010; 31(6):613-22. DOI: 10.1007/s13277-010-0077-x. View

19.

Terrovitis J, Kwok K, Lautamaki R, Engles J, Barth A, Kizana E . Ectopic expression of the sodium-iodide symporter enables imaging of transplanted cardiac stem cells in vivo by single-photon emission computed tomography or positron emission tomography. J Am Coll Cardiol. 2008; 52(20):1652-60. PMC: 4980098. DOI: 10.1016/j.jacc.2008.06.051. View

20.

Xu X, Yang G, Zhang H, Prestwich G . Evaluating dual activity LPA receptor pan-antagonist/autotaxin inhibitors as anti-cancer agents in vivo using engineered human tumors. Prostaglandins Other Lipid Mediat. 2009; 89(3-4):140-6. PMC: 2756011. DOI: 10.1016/j.prostaglandins.2009.07.006. View