Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Apr 27, 2020; 10(3): 26-40
Published online Apr 27, 2020. doi: 10.5493/wjem.v10.i3.26
Isolation and identification of adipose-derived stromal/stem cells from breast cancer patients after exposure neoadjuvant chemotherapy
Ashleigh Rapp Hagaman, Ping Zhang, Kiavash R Koko, Ryan S Nolan, Marc W Fromer, John Gaughan, Martha Matthews
Ashleigh Rapp Hagaman, Ping Zhang, Kiavash R Koko, Ryan S Nolan, Marc W Fromer, John Gaughan, Martha Matthews, Department of Surgery, Cooper University Hospital, Camden, NJ 08103, United States
Ping Zhang, John Gaughan, Martha Matthews, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
Author contributions: Hagaman AR and Zhang P performed conception and design, collected samples, the majority of experiments, analyzed the data and wrote the article; Koko KR, Nolan RS and Fromer MW collected samples, clinical analysis, and interpretation; Matthews M performed conception and design, patients selection and collected samples, clinical analysis, and interpretation; Gaughan J, a senior biostatistician performed study statistical analysis.
Institutional review board statement: All patients provided written informed consent in accordance with our IRB-approved protocol by Cooper Health Care Institutional Review Board (Protocol approval number # 15-107EX/2015, name: Examining the potential impact of chemotherapy and radiation on mesenchymal stem cells in cancer patients).
Conflict-of-interest statement: The authors declare that there is no conflict of interest regarding the publication of this paper.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ping Zhang, DDS, PhD, Assistant Professor, Department of Surgery, Cooper University Hospital, Cooper Medical School of Rowan University, 401 Haddon Avenue, Camden, NJ 08103, United States. zhang-ping@cooperhealth.edu
Received: December 9, 2019
Peer-review started: December 9, 2019
First decision: December 26, 2019
Revised: February 4, 2020
Accepted: March 28, 2020
Article in press: March 28, 2020
Published online: April 27, 2020
Abstract
BACKGROUND

With recent research advances, adipose-derived stromal/stem cells (ASCs) have been demonstrated to facilitate the survival of fat grafts and thus are increasingly used for reconstructive procedures following surgery for breast cancer. Unfortunately, in patients, following radiation and chemotherapy for breast cancer suggest that these cancer treatment therapies may limit stem cell cellular functions important for soft tissue wound healing. For clinical translation to patients that have undergone cancer treatment, it is necessary to understand the effects of these therapies on the ASC's ability to improve fat graft survival in clinical practice.

AIM

To investigate whether the impact on ASCs function capacity and recovery in cancer patients may be due to the chemotherapy.

METHODS

ASCs were isolated from the cancerous side and noncancerous side of the breast from the same patients with receiving neoadjuvant chemotherapy (NAC) or not-receiving NAC. ASCs were in vitro treated with 5-fluorouracil (5-FU), doxorubicin (DXR), and cyclophosphamide (Cytoxan) at various concentrations. The stem cells yield, cell viability, and proliferation rates were measured by growth curves and MTT assays. Differentiation capacity for adipogenesis was determined by qPCR analysis of the specific gene markers and histological staining.

RESULTS

No significant differences were observed between the yield of ASCs in patients receiving NAC treatment and not-receiving NAC. ASCs yield from the cancerous side of the breast showed lower than the noncancerous side of the breast in both patients receiving NAC and not-receiving NAC. The proliferation rates of ASCs from patients didn’t differ much before and after NAC upon in vitro culture, and these cells appeared to retain the capacity to acquire adipocyte traits simile to the ASCs from patients not-receiving NAC. After cessation and washout of the drugs for another a week of culturing, ASCs showed a slow recovery of cell growth capacity in 5-FU-treated groups but was not observed in ASCs treated with DXR groups.

CONCLUSION

Neoadjuvant therapies do not affect the functioning capacity of ASCs. ASCs may hold great potential to serve as a cell source for fat grafting and reconstruction in patients undergoing chemotherapy.

Keywords: Human adipose-derived stromal/stem cells, Breast cancer, Neoadjuvant chemotherapy, Chemotherapeutic agents, Adipogenic differentiation, Proliferation

Core tip: The functioning capacity and recovery potential of adipose-derived mesenchymal stromal/stem cells (ASCs) were demonstrated in terms of the stem cell yield, proliferation rates and adipogenic differentiation capabilities in breast cancer patients after exposure to neoadjuvant therapies (NAC) treatment. The yield of ASCs did not alter much after NAC treatment of patients. Moreover, the proliferation rates of ASCs derived from patients didn’t differ much before and after NAC upon in vitro culture, and these cells appeared to retain the differentiation capacity to acquire adipocyte traits simile to those ASC obtained from the patients not-receiving NAC.