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
ARTICLE HIGHLIGHTS
Research background

In cancer patients, post-exposure to radiation and chemotherapy suggests that these cancer treatment therapies may limit stem cells 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 adipose-derived stromal/stem cell (ASC)'s ability to improve fat graft survival in clinical practice. Herein, we examined the effects of chemotherapy on ASCs outcomes in patients with receiving neoadjuvant therapies and compared to the patients not-receiving neoadjuvant chemotherapy (NAC) treatment.

Research motivation

Recent research has focused almost entirely on poor soft tissue wound healing in patients exposure to radiation/or chemotherapy, but little is known about the recovery of cell viability and function capability of stem cells in patients receiving chemotherapeutic-treatment. This research focused on characteristics of stem cells isolated from human adipose tissue: (1) The cellular function of ASCs diminished in direct exposure to chemotherapeutic agents, and potency to recovery after cessation of these drugs in treatment; and (2) Availability in receiving NAC treatment of population most likely the ASCs may hold great potential to serve as a cell source for fat grafting and reconstruction in cancer patients undergoing chemo-treatment. This research will provide new and novel insight information regarding the use of autologous mesenchymal stem cells derived from adipose tissue in cancer patients after exposure to chemotherapy.

Research objectives

The main objective of this study was to investigate whether the impact on ASCs function capacity and recovery in cancer patients may be due to the chemotherapy. In addition, we evaluated in vitro, whether ASCs have the potential for recovery of cellular function after exposure to three commonly utilized clinical chemotherapeutic agents.

Research methods

We analyzed the stem cells yield, proliferation rates, and adipogenesis differentiation capacity of ASCs from breast cancer patients with receiving NAC treatment or not-receiving NAC. We also measured the recovery of the cellular functions of ASCs after treated with three chemotherapeutic agents by in vitro culture system.

Research results

We reveal that the yield of ASCs didn’t alter much after NAC treatment of patients. 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 capacity to acquire adipocyte traits simile to the ASCs that from patients not-receiving NAC. By observing the in vitro culture system, the study indicates that the full recovery of cell proliferation rates was not observed in ASCs after the withdrawal of drug treatment in a short time interval.

Research conclusions

We conclude that (1) the availability of ASCs for use does not appear to be adversely affected by post-chemotherapy; (2) despite the in vitro evidence of the negative effects of chemotherapeutic agents on the ASCs, it might not be clinically relevant as ex vivo examination of patient’s ASC shows these cells can functionally recover after various neoadjuvant chemotherapy regimens; and (3) the breast adipose tissue appears to will be a viable source of autologous stem cells and ASCs may hold great potential and represents to serve as a cell source for use in fat grafting and reconstruction in patients undergoing chemotherapy such as in breast cancer patients.

Research perspectives

The study of our results provides novel insight into the use of autologous stem cell-based target therapy in reconstructive procedures in cancer patients that have received chemotherapy. Further study is needed to determine the temporal effects of chemotherapy before, during chemo-treatment and after cessation to evaluate ASC function and recovery potential in patients to clarify whether the impact on ASC function and recovery components may be due to the chemotherapy.