Single Cells, Infinite Possibilities

Authored by: Katie Greening

Art by: Kain Wang

While it may be impossible to create something from absolutely nothing, new advancements in medicine bring us very close. Regenerative medicine, which is the study of repairing and replacing damaged cells in the body, is a rapidly developing field. Through stem cell therapy, gene editing, and tissue engineering, conditions once thought incurable are now becoming less of lifelong barriers, and more like challenges medicine can overcome– not just treating damaged tissues in adults, but also incomplete development in preterm infants. 

Stem cells are among the most important elements driving regenerative medicine, and have the potential to differentiate into almost any cell found in the human body. They come in many different forms, including embryonic stem cells (ESCs) taken from the inner cell mast of a blastocyst, and induced pluripotent stem cells (iPSCs), previously somatic stem cells reprogrammed for pluripotency [1]. These types of cells aid in tackling the challenge of immune rejection in organ transplants, as well as the persistent shortage of the organs themselves. Stem cell therapies are among the most common applications of regenerative medicine, and significantly reduce the risk of immune rejection as they are sourced by sourcing stem cells directly from the patients [2].

Therapies using embryonic, induced pluripotent, limbal, neural, and placental stem cells are showing promising results in clinical trials, with the potential to treat conditions such as heart failure, stroke, and immune disorders [3]. Mesenchymal cells, in particular, are prominent in stem cell therapies. Umbilical cord blood has been found to have great potential in treating disorders like paraplegia, cerebrovascular disease, and even amyotrophic lateral sclerosis– a condition first identified in the late 1800s that has gone without a cure for over a century [4][5]. Many of these therapies are also minimally invasive, with treatments for damaged or diseased tissues of the heart only requiring a simple injection of stem cells into the damaged region [2]. 

While much of regenerative medicine is focused on repairing and regenerating old or damaged tissue, it has its applications in neonatal conditions as well. Preterm births are becoming increasingly common, but recent medical advances, including advances in regenerative medicine, have helped  to increase the survival rate of preterm births as well. Bronchopulmonary dysplasia (BPD) is the most prevalent lung disorder in preterm babies, and is characterized by the incomplete development of the lungs, particularly in the alveoli and the vasculature [6][7]. Due to the nature of this disease, regenerative stem cell therapies prove to be a promising approach, as they commonly aim to promote cell proliferation rather than attempting a full lung transplant, which can be invasive and risky.  Mesenchymal stem cells (MSCs) derived from bone marrow are what is typically used in stem-cell therapies for BPD, though they can also be extracted from fat, cord blood, and the placenta. More specifically, since BPD is a result of incomplete bronchopulmonary development rather than the MSCs fixing damaged tissue– a common form of stem cell therapy– they promote alveolarization and angiogenesis through paracrine signaling. The MSCs administered through intravenous, intratracheal, intraperitoneal, or intranasal routes secrete growth factors that allow bronchopulmonary development to continue under suboptimal conditions [7]. 

However, the field is still in its early stages, with major obstacles yet to be overcome. Many proposed therapies still have not moved past the animal-model testing phase, and the risk of immunological rejection by the patient’s immune system still stands [1]. Furthermore, a popular approach to generating artificial organs from stem cells involves growing them inside host animals, which raises important ethical questions about the use of mammals such as rats and pigs for this purpose [8]. Lastly, especially in cases that involve birth defects and conditions in preterm infants, researchers must weigh the potential to save lives against the risks of exposing those most vulnerable to unproven treatments. 

References

1. Zakrzewski, W., Dobrzyński, M., Szymonowicz, M. et al. (2019). Stem cells: past, present, and future. Stem Cell Res Ther, Vol. 10, 68 https://doi.org/10.1186/s13287-019-1165-5

2. Atala A. (2012). Regenerative medicine strategies, Journal of Pediatric Surgery, Vol. 47, 17-28. https://doi.org/10.1016/j.jpedsurg.2011.10.013.

3. Trounson, A., & McDonald, C. (2015). Stem Cell Therapies in Clinical Trials: Progress and Challenges. Cell stem cell, 17(1), 11–22. https://doi.org/10.1016/j.stem.2015.06.007

4. Trounson, A., Thakar, R.G., Lomax, G. & Gibbons. D. (2011). Clinical trials for stem cell therapies. BMC Med, Vol. 9, 52 https://doi.org/10.1186/1741-7015-9-52

5. Rowland L. P. (2001). How amyotrophic lateral sclerosis got its name: the clinical-pathologic genius of Jean-Martin Charcot. Archives of neurology, 58(3), 512–515. https://doi.org/10.1001/archneur.58.3.512

6. Kinsella, J. P., Greenough, A., & Abman, S. H. (2006). Bronchopulmonary dysplasia. Lancet (London, England), 367(9520), 1421–1431. https://doi.org/10.1016/S0140-6736(06)68615-7

7. Omar, S. A., Abdul-Hafez, A., Ibrahim, S., Pillai, N., Abdulmageed, M., Thiruvenkataramani, R. P., Mohamed, T., Madhukar, B. V., & Uhal, B. D. (2022). Stem-Cell Therapy for Bronchopulmonary Dysplasia (BPD) in Newborns. Cells, 11(8), 1275. https://doi.org/10.3390/cells11081275

8. Tam, P. K. H., Wong, K. K. Y., Atala, A., Giobbe, G. G., Booth, C., Gruber, P. J., Monone, M., Rafii, S., Rando, T. A., Vacanti, J., Comer, C. D., Elvassore, N., Grikscheit, T., & de Coppi, P. (2022). Regenerative medicine: postnatal approaches. The Lancet. Child & adolescent health, 6(9), 654–666. https://doi.org/10.1016/S2352-4642(22)00193-6