The future of mesenchymal stem cell-based therapeutic approaches for cancer – From cells to ghosts

Abstract

Mesenchymal stem cells (MSCs) are multipotent stromal cells which can differentiate into a variety of cell types including osteoblasts, adipocytes and chondrocytes. They are normally resident in adipose tissue, bone marrow and the umbilical cord, but can also be found in other tissues and are known to be recruited to sites of wound healing as well as growing tumours. The therapeutic potential of MSCs has been explored in a number of phase I/II and III clinical trials, of which several were targeted against graft-versus-host disease and to support engraftment of haematopoietic stem cells (HSCs), but currently only very few in the oncology field. There are now three clinical trials either ongoing or recruiting patients that use MSCs to treat tumour disease. In these, MSCs target gastrointestinal, lung and ovarian cancer, respectively. The first study uses MSCs loaded with a HSV-TK expression construct under the control of the CCL5 promoter, and has recently reported successful completion of Phase I/II. While no adverse side effects were seen during this study, no outcomes with respect to therapeutic benefits have been published. The other clinical trials targeting lung and ovarian cancer will be using MSCs expressing cytokines as therapeutic payload. Despite these encouraging early steps towards their clinical use, many questions are still unanswered regarding the biology of MSCs in normal and pathophysiological settings. In this review, in addition to summarising the current state of MSC-based therapeutic approaches for cancer, we will describe the remaining questions, obstacles and risks, as well as novel developments such as MSC-derived nanoghosts.

WITHDRAWN: Anti-Oncogenic Activities Exhibited By Secretomes Of Mesenchymal Stem Cells Are Mediated By Modulation Of KITLG and DKK1 Genes In Glioma Stem Cells.

“…New treatment modalities, including novel agents and small molecule inhibitors, are currently under investigation. Remotely, mesenchymal stem cells (MSCs) and their soluble factors are reported to exhibit bene cial anticancer effects (49,50,51). In order to investigate further if the soluble factors of MSCs may affect different pathways related to proliferation and stemness of GSC to transform them into non-stem-like cells prone to therapies, we planned this study.…”

Pretreating Mesenchymal Stem Cells with Cancer Conditioned‐Media or Proinflammatory Cytokines Changes the Tumor and Immune Targeting by Nanoghosts Derived from these Cells

“…Nanoghosts (NGs) is a proprietary novel form of a targeted delivery platform, which is based on nanovesicles that are technologically reconstructed from the whole cytoplasmic membranes of human bone marrow‐derived mesenchymal stem cells (MSCs). Initially developed for tumor‐targeted drug delivery, NGs were recognized as one of the few technologies that can realize the translational potential of MSCs in oncology . This recognition was owed to previous reports demonstrating the ability of the NGs to selectively deliver diverse therapeutics into pancreatic, lung, breast, and other tumor models with exceptional therapeutic outcomes .…”

Modeling Adipogenesis: Current and Future Perspective

“…For this reason, ADSCs have been clinically used in treatments for inflammatory and autoimmune diseases, such as in trials of graft versus host rejection, Crohn’s disease, and multiple sclerosis [ 81 , 82 ]. The use of these cells as cancer therapies still remains controversial because of their immunomodulatory behavior, which could lead to more growth and a higher metastatic potential [ 83 ]. It is worth noting, however, that ADSCs taken from obese individuals have reduced differentiation, immunomodulatory, anti-inflammatory, and metabolic functions [ 84 ].…”