About this Research Topic

Background

Stem cell therapies have the potential for widespread tissue regeneration of injured or diseased tissues and cures for chronic and inflammatory diseases. During local injury, endogenous stem cells can be activated and recruited to the injury site to exert their pro-regenerative effects by secreting bioactive molecules and modulating the immune response. Stem cells can serve as in vivo drug stores utilising the combination of these bioactive factors and immunomodulatory activities.

The therapeutic benefits of stem cells are now widely believed to come from their paracrine effects, i.e. secreted factors such as cytokines, chemokines, extracellular vesicles and so on. We predict the future cell therapies will rely on these factors instead of whole cells.

This Research Topic aims to bring together experts in the stem cells and regenerative medicine field to identify emerging technologies that utilise these properties of stem cells. We invite stem cell scientists, pharmacologists, biomaterial scientists, biomedical engineers, bioprocess engineers, regulatory experts, healthcare professionals to contribute basic Research papers, Clinical papers, and Review articles.

Submissions covered in this Research Topic include:
1. Stem cells as drug factories for therapeutic factors
There is an increasing recognition that stem cells are excellent candidates for natural drug delivery vehicles, owing to their intrinsic therapeutic properties, potential for genetic modification, and scalability for GMP manufacturing process.

2. Genetic engineering of stem cells for tissue regeneration
Genetic modification can amplify and broaden therapeutic properties of stem cells; however, special care must be placed on the characterisation to tailor these cells to specific diseases. Examples of approaches could include overexpression or knockdown of membrane proteins, cytoplasmic proteins, transcription factor genes, microRNAs, secreted growth factors, and nucleus-acting proteins.

3. Bioengineering cell microenvironment to improve their paracrine activity
The microenvironment surrounding stem cells is critical to produce the necessary factors that mediate the desired therapeutic effects. Microenvironmental conditions such as soluble factors, oxygen tension, 3D culture, matrix stiffness, mechanical stimulation, ECM composition will impact stem cells’ paracrine activity and enable us to control their therapeutic payloads.

4. Next generation scalable biomanufacturing of stem cells and/or stem cells' secretome
The current bottleneck facing the clinical translation of stem cell therapies includes the expansion of large numbers of stem cells, maintenance of the stem cell phenotype, and failure of clinical grade stem cells to replicate effects of research grade stem cells.

5. Nanoparticles/nanomedicine in regenerative medicine
Natural or engineered nanoparticles are frequently utilised to release bioactive cargo in a controlled manner. Specifically, stem cell-derived extracellular vesicles have emerged as a promising candidate for cell-free therapeutics and these can be engineered in a similar way to nanoparticles and synthetic liposomes.

6. Novel biomaterials for stem cells and targeted drug delivery
During cell transplantation, cell delivery via needle subjects the cells to significant mechanical damage thus causing reduction in cell viability and failure to engraft. Advances in biomaterials tailored for cell delivery systems would overcome this problem and also increase stem cell or growth factor retention following injection.

7. Regulatory aspects to use stem cell-derived products in the clinic
The rapidly developing cell therapy market will bring several regulatory challenges for drug development, scalable manufacturing, commercialisation, and patient safety. From a regulatory point of view, the main challenges revolve around definition of the mechanism of action, the optimum pharmaceutical dose and standardised release criteria for stem cell products.


Topic Editor RL is a patent inventor on exosome related patents, PCT/AU2017/050821 and PCT/AU2016/050468. All other Topic Editors declare no competing interests with regards to the Research Topic subject.

Keywords: Stem cells, cell therapies, drug delivery, regenerative medicine, extracellular vesicles

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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