Exosomes Derived from Induced and Wharton's Jelly-Derived Mesenchymal Stem Cells Promote Senescence-like Features and Migration in Cancer Cells

Abstract

Mesenchymal stem cell-derived exosomes (MSC-Exos) play a key role in tissue repair, immune regulation, and cancer biology. Due to limitations in MSC expansion and source variability, interest has shifted to induced pluripotent stem cell-derived MSCs (iMSCs) as a promising alternative. This study compares effects of exosomes derived from iMSCs (iMSC-Exos) and Wharton's jelly MSCs (WJMSC-Exos) on MCF7 and A549 cancer cells. Both types of exosomes reduced MCF7 proliferation and induced a senescence-like state, rather than apoptosis, although the antiproliferative effect was transient in A549 cells. Notably, WJMSC-Exos promoted migration in both MCF7 and A549, whereas iMSC-Exos did not exhibit this effect. Overall, WJMSC-Exos had a more robust impact on cancer cell proliferation and migration. These findings highlight the diverse effects of exosomes on cancer and the development of a senescence-like state as an important response to Exos exposure. Moreover, these findings invite for more careful evaluation of the therapeutic role of iMSC-derived Exos.

Keywords: Wharton’s jelly-derived mesenchymal stem cells (WJMSCs); cancer; cell-free therapy; exosomes; induced mesenchymal stem cells (iMSCs); senescence.

Figure 1

Evaluation of proliferation and apoptosis in MCF7 and A549 cells treated with iMSC-Exos or WJMSC-Exos. (A) Internalization of iMSC- and WJMSC-Exos by MCF7 and (B) A549 cancer cells. MTT assay in (C) MCF7, (D) A549 and (E) fibroblast cells treated with iMSC- and WJMSC-derived Exos. Statistical analysis of the percentage of Q1 (necrotic cells), Q2 (late apoptotic cells), Q3 (live cells), and Q4 (early apoptotic cells) in (F) MCF7 cells and (G) A549 cells. Data are represented as mean ± SD. * p ≤ 0.05, ** p ≤ 0.01, **** p ≤ 0.0001.

Figure 2

Examination of senescence-associated markers in MCF7 and A549 cells treated with exosomes. ((A) & (C)) Representative microscopic images of senescent cells (green) in MCF7 (upper left) and A549 (lower left). ((B) & (D)) Quantification of senescent cell percentages following treatment with iMSC-derived or WJMSC-derived exosomes for MCF7 cells (top right) and A549 cells (bottom right) cells. Expression levels of senescence-associated genes in MCF7 and A549 cells treated with iMSC- or WJMSC-derived Exos: (E) p53, (F) p21^Cip1, (G) CXCL8, (H) IL-6, (I) TNF-α, and (J) TGF-β1. All Data are expressed as mean ± SD. Statistical significance is indicated as ns (not significant), * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001 and **** p ≤ 0.0001.

Figure 3

Assessment of migration potential of MCF7 and A549 cells treated with exosomes. Representative microscopic images of wound healing (WH) following a scratch assay are shown for (A) MCF7 cells and (C) A549 cells. The migration area of (B) MCF7 and (D) A549 cells treated with either iMSC- or WJMSC-derived exosomes was measured at approximately 9-, 20-, and 47-h post-scratch. Data are presented as mean ± SD. Statistical significance is indicated as * p ≤ 0.05, ** p ≤ 0.01, and **** p ≤ 0.0001.