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Wound Microenvironment Sequesters Adipose-Derived Stem Cells in a Murine Model of Reconstructive Surgery in the Setting of Concurrent Distant Malignancy

Altman, Andrew M. M.D.; Prantl, Lukas M.D., Ph.D.; Muehlberg, Fabian L.; Song, Yao-Hua M.D., Ph.D.; Seidensticker, Max M.D.; Butler, Charles E. M.D.; Alt, Eckhard U. M.D., Ph.D.

Plastic & Reconstructive Surgery: April 2011 - Volume 127 - Issue 4 - pp 1467-1477
doi: 10.1097/PRS.0b013e31820a6400
Experimental: Original Articles

Background: It is unclear whether mesenchymal stem cells that are applied to regenerate wound tissues can migrate to existing tumors and enhance their growth. The authors investigated whether adipose-derived stem cells had any effect on the growth and progression of distant tumors when applied to a skin wound.

Methods: The authors subcutaneously injected murine 4T1 breast cancer cells into all BALB/c-nu/nu mice. After tumor injection, mice were randomized to five groups (five mice per group) based on the means of co-introduction of green fluorescent protein–labeled adipose-derived stem cells, if any. In group 1, adipose-derived stem cells were combined and co-injected subcutaneously. In group 2, they were injected subcutaneously at a distant anatomical site. In group 3, they were injected intravenously. In group 4, they were delivered via a human acellular dermal matrix to a distant skin wound. In group 5, no adipose-derived stem cells were introduced.

Results: After 2 weeks, tumor volume increased in group 1 (356.5 ± 44.4 mm3), followed by group 3 (256.6 ± 47.1 mm3) and then group 2 (201.6 ± 28.6 mm3). In group 4, in which adipose-derived stem cells carried on acellular dermal matrix were applied to a wound distant to the primary tumor, the tumor volume was 143.8 ± 50.9 mm3, which was similar to that observed in the control group (group 5; 167.8 ± 29.9 mm3).

Conclusions: The authors' findings suggest that the wound microenvironment can retain adipose-derived stem cells, preventing their homing and stromal contribution to a distant neoplastic focus. These findings are an important first step in establishing the feasibility and safety of utilizing adipose-derived stem cell therapy for reconstructive surgery in the setting of malignancy.

Houston, Texas; and Regensburg and Magdeburg, Germany

From the Departments of Molecular Pathology and Plastic Surgery, University of Texas M. D. Anderson Cancer Center; Division of Plastic and Reconstructive Surgery, Universitaetsklinikum; and Department of Radiology, Otto von Guericke University.

Received for publication May 13, 2010; accepted October 5, 2010.

Dr. Altman and Dr. Prantl contributed equally to this work.

Disclosure: Dr. Butler serves as a consultant for LifeCell. Dr. Alt is a board member of InGeneron Inc. The other authors have no financial information to disclose.

Eckhard U. Alt, M.D., Ph.D.; Department of Molecular Pathology, Unit 951; University of Texas M. D. Anderson Cancer Center; 7435 Fannin Street; Houston, Texas 77054

Charles E. Butler, M.D.; Department of Plastic Surgery, Unit 443; University of Texas M. D. Anderson Cancer Center; 1515 Holcombe Boulevard; Houston, Texas 77030; cbutler@mdanderson.org

©2011American Society of Plastic Surgeons