Faculty Collaboration Database

Human mesenchymal stromal cells do not promote recurrence of soft tissue sarcomas in mouse xenografts after radiation and surgery. Cytotherapy 2018 Aug;20(8):1001-1012

Date

08/05/2018

Pubmed ID

30076069

DOI

10.1016/j.jcyt.2018.05.011

Scopus ID

2-s2.0-85050668188 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

BACKGROUND: Mesenchymal stromal cells (MSCs) promote wound healing, including after radiotherapy (RT) and surgery. The use of MSCs in regenerative medicine in the context of malignancy, such as to enhance wound healing post-RT/surgery in patients with soft tissue sarcomas (STSs), requires safety validation. The aim of this study was to determine the effects of human MSCs on STS growth in vitro and local recurrence and metastasis in vivo.

METHODS: Human primary STS and HT-1080 fibrosarcoma lines were transduced to express luciferase/eGFP (enhanced green fluorescent protein). Sarcoma cells were co-cultured or co-injected with bone marrow-derived MSCs for growth studies. Xenograft tumor models were established with STS lines in NOD/SCID/γ_c^null mice. To emulate a clinical scenario, subcutaneous tumors were treated with RT/surgery prior to MSC injection into the tumor bed. Local and distant tumor recurrence was studied using histology and bioluminescence imaging.

RESULTS: MSCs did not promote STS proliferation upon co-culture in vitro, which was consistent among MSCs from different donors. Co-injection of MSCs with sarcoma cells in mice exhibited no significant tumor-stimulating effect, compared with control mice injected with sarcoma cells alone. MSC administration after RT/surgery had no effect on local recurrence or metastasis of STS.

DISCUSSION: These studies are important for the establishment of a safety profile for MSC administration in patients with STS. Our data suggest that MSCs are safe in STS management after standard of care RT/surgery, which can be further investigated in early-phase clinical trials to also determine the efficacy of MSCs in reducing morbidity and to mitigate wound complications in these patients.

Author List

Filomeno PA, Kim KP, Yoon N, Rashedi I, Dayan V, Kandel RA, Wang XH, Felizardo TC, Berinstein E, Jelveh S, Filomeno A, Medin JA, Ferguson PC, Keating A

Author

Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Animals
Coculture Techniques
Combined Modality Therapy
HEK293 Cells
Heterografts
Humans
Male
Mesenchymal Stem Cell Transplantation
Mice
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Neoplasm Recurrence, Local
Radiotherapy
Sarcoma
Surgical Procedures, Operative
Tumor Cells, Cultured
Wound Healing
Xenograft Model Antitumor Assays