Articles

Introduction 

Since the inception of regenerative medicine in the late 20th century, numerous regenerative medicine therapies, including those designed for wound healing and orthopedic applications, have received FDA approval and are now commercially available. In this article, we introduce representative key fields currently being studied and explore current progress of regenerative medicine. Together with our earlier article, we aim to provide a solid introduction for a more in-depth understanding of the field.

Representative key fields of regenerative medicine 

Regenerative medicine is an interdisciplinary field that brings together experts in biology, chemistry, computer science, engineering, genetics, medicine, robotics, and other fields to address some of the most significant challenges in modern medicine. Regenerative medicine can be broadly divided into three representative key fields: cellular therapy, tissue engineering, and medical devices.

Cellular therapy

General overview

Stem cells play a key role in maintaining the body by supplying new differentiated cells. Stem cell therapies are expected to bring substantial benefit to patients suffering a wide range of diseases and injuries by using adult stem cells or pluripotent stem cells. Not only pluripotent stem cells (ESCs or iPSCs) but also adult stem cells (hematopoietic stem cells, neural stem cells, epithelial stem cells, etc.)  have been well studied for clinical application [1]. The delivery of therapeutic cells that directly contribute to the structure and function of new tissues is a primary paradigm of regenerative medicine to date [2].

Current progress

ESCs and iPSCs are making their way into clinical trials to treat a wide range of diseases such as macular degeneration, heart failure, and Parkinson’s disease [1]. 

Studies on adult stem/progenitor cells have also progressed in the field of anti-aging, and have revealed that these immature and regenerative cells with a high longevity provide critical functions in maintaining skin homeostasis and repair after severe injuries along the lifespan of individuals [3]. These future investigations should help to develop new anti-aging strategies for preventing or delaying the onset of age-related skin disorders in human beings.

Tissue engineering 

General overview 

Approximately 40 years ago, tissue engineering emerged as an alternative approach to tissue and organ reconstruction [4]. Tissue engineering is a strategy for the replacement of damaged tissue with living tissue that is designed and tailored to each patient’s specific needs. A distinctive feature of tissue engineering is regenerating patient's own tissues and organs that are entirely free from issues of poor biocompatibility and low biofunctionality as well as severe immune rejection [5]. 

Current progress

The most important developments in tissue engineering are the use of three-dimensional (3D) bioprinting, and organs-on–a-chip (OoC) technologies [6]. 

3D bioprinting enables the creation of thicker human tissues replete with an engineered extracellular matrix, embedded vasculature, and multiple cell types in vivo [7]. 

OoC takes the form of a microfluidic device containing networks of microscale channels for guiding and manipulating minute volumes (picoliters up to milliliters) of solution. Although these tissues on a chip are much simpler than native tissues and organs, scientists have discovered that this system can often serve as effective models of human physiology and disease [8]. 

Medical devices and biomaterials 

General overview

While cell biological discoveries have developed rapidly, medical devices and biomaterials remain essential components in clinical applications. In cases where an organ fails, medical devices are required to support or supplement the function of the failing organ until a transplantable organ is found. Furthermore, studies of medical devices and biomaterials have contributed to regenerative medicine by serving scaffolds to deliver cells, providing biological signals and physical support, and mobilizing endogenous cells to repair tissues [9].

Current progress

While drugs and biologics can require more than a dozen years of development and testing for the progression from concept to market, medical devices generally reach the market after only 3–7 years of development and may undergo an expedited process if they are demonstrated to be similar to pre-existing devices [2]. Due to the less arduous approval process, medical device products may be preferable from a regulatory and development perspective, compared with cell-based products.l 

Conclusion 

Together with our earlier article, we introduced the crucial point and the representative key fields of regenerative medicine. Regenerative medicine has great potential in tailored clinical treatment and anti-aging. We will focus on how to utilize regenerative medicine in anti-aging.

Reference

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2. Mao, A. S., & Mooney, D. J. (2015). Regenerative medicine: Current therapies and future directions. Proceedings of the National Academy of Sciences of the United States of America, 112(47). https://doi.org/10.1073/pnas.1508520112

3. Mimeault, M., & Batra, S. K. (2010). Recent advances on skin-resident stem/progenitor cell functions in skin regeneration, aging and cancers and novel anti-aging and cancer therapies. In Journal of Cellular and Molecular Medicine(Vol. 14, Issues 1–2). https://doi.org/10.1111/j.1582-4934.2009.00885.x

4. Vacanti, J. P., & Langer, R. (1999). Tissue engineering: The design and fabrication of living replacement devices for surgical reconstruction and transplantation. Lancet, 354(SUPPL.1). https://doi.org/10.1016/s0140-6736(99)90247-7

5. Ikada, Y. (2006). Challenges in tissue engineering. In Journal of the Royal Society Interface (Vol. 3, Issue 10). https://doi.org/10.1098/rsif.2006.0124

6. Ashammakhi, N., Ghavaminejad, A., Tutar, R., Fricker, A., Roy, I., Chatzistavrou, X., Hoque Apu, E., Nguyen, K. L., Ahsan, T., Pountos, I., & Caterson, E. J. (2022). Highlights on Advancing Frontiers in Tissue Engineering. In Tissue Engineering - Part B: Reviews (Vol. 28, Issue 3). https://doi.org/10.1089/ten.teb.2021.0012

7. Kolesky, D. B., Homan, K. A., Skylar-Scott, M. A., & Lewis, J. A. (2016). Three-dimensional bioprinting of thick vascularized tissues. Proceedings of the National Academy of Sciences of the United States of America, 113(12). https://doi.org/10.1073/pnas.1521342113

8. Leung, C. M., de Haan, P., Ronaldson-Bouchard, K., Kim, G. A., Ko, J., Rho, H. S., Chen, Z., Habibovic, P., Jeon, N. L., Takayama, S., Shuler, M. L., Vunjak-Novakovic, G., Frey, O., Verpoorte, E., & Toh, Y. C. (2022). A guide to the organ-on-a-chip. In Nature Reviews Methods Primers (Vol. 2, Issue 1). https://doi.org/10.1038/s43586-022-00118-6

9. Holzapfel, B. M., Reichert, J. C., Schantz, J. T., Gbureck, U., Rackwitz, L., Nöth, U., Jakob, F., Rudert, M., Groll, J., & Hutmacher, D. W. (2013). How smart do biomaterials need to be? A translational science and clinical point of view. In Advanced Drug Delivery Reviews (Vol. 65, Issue 4). https://doi.org/10.1016/j.addr.2012.07.009