Articles

Intoduction

The promising field of regenerative medicine is working toward the restoration of structure and function in damaged tissues and organs. It is also working to integrate stem cell biology with personalized therapeutic, diagnostic, prognostic, and preventive solutions across human diseases, providing a cornerstone of modern tailored medicine practice.

 

In this article, we feature the history of regenerative medicine, and introduce basic concepts for a wide variety of readers interested in this field. This article aims to be a good starting point for a more in-depth understanding of regenerative medicine.

History of regenerative medicine

Why is regenerative medicine required?

Over the past centuries, medicine has made significant advances. However, many conditions still cannot be treated while preserving the affected organs, but require the resection of legions, the repair with autologous or the replacement with allografts. This is “the three R’s paradigm” in traditional surgery with three solutions, all of which pose different problems [1]. A great deal of research has grown up regenerative medicine as “the fourth R” that replaces or regenerates human cells, tissues or organs, to restore or establish normal function.

The historical summary of regenerative medicine

1930s : Creation of the concept of artificial organs

Regenerative medicine is considered a novel frontier of medical research, but the idea of creating artificial organs is not so recent. In 1938, Alexis Carrel, a Nobel Prize winner for his study on vascular anastomosis, and Charles Lindbergh, the first aviator to fly across the Atlantic alone, had already published a book, called “The culture of new organs” [2]. Their work contributed to creating the basis of artificial organs, and also regenerative medicine.

1950s to 1980s : The first successes in cell transplantation

Clinical transplantation advanced by the discoveries about immunosuppression in the 1950s.  And the first successful bone marrow transplantations in humans followed in the end of the 1960s [3]. 

After many studies in the field of clinical transplantation, engineered tissue transplantation for the treatment of extensive burn injury succeeded for the first time in 1981 [4]. It was also the key event that led to the foundation of tissue engineering. 

1990s to 2010s: Advance of stem cell research and tissue engineering 

The successes in establishment of human embryonic stem (ES) cell lines and embryonic germ (EG) cell lines in 1998 were the most significant breakthroughs of the century, even if these findings raised sharp ethical and political controversies [5][6]. 

And, induced pluripotent stem (iPS) cells were derived from reprogrammed adult somatic cells with just four basic transcription factors in 2007 [7]. The discovery of iPS cells impacted many researchers, because iPS cells have the same cell potency as ES cells, and can be used for the generation of disease-specific lines to study disease mechanisms and drug screening. Research in iPS cells remains the most prominent area in the field of regenerative medicine today [8].

Overview of regenerative medicine

What is regenerative medicine?

The term “regenerative medicine” is widely considered to be coined during a 1999 conference on Lake Como, in the attempt to describe an emerging field which blent knowledge deriving from various fields: tissue engineering, cell transplantation, stem cell biology, etc. Because it would become a little abundant if we explain the details at once, we introduce the key word essential for understanding regenerative medicine in this article. 

What are stem cells?

Stem cells are key players maintaining almost all tissues and organs, and are characterized by the ability to extensively proliferate (self-renewal), usually arise from a single cell (clonal), and differentiate into different types of cells and tissue (potent) [9].  Stem cells can be categorized according to their differentiation potential into 5 groups: totipotent, pluripotent, multipotent, oligopotent, and unipotent. 

ES cells are stem cells derived from the early embryo that can be propagated indefinitely in the primitive undifferentiated state while remaining pluripotent; they share these properties with EG cells [10]. 

In principle, developmental potency of the cell is reduced with each step. In this regard, iPS cells are special because they proved that mature cells can be reprogrammed to pluripotent state by gene transfer artificially [11].

Conclusion 

In this article, we introduced the crucial point of regenerative medicine history.

We will explain details of representative fields of regenerative medicine in the next article. We will do our best to provide a good starting point for your understanding of regenerative medicine.

Reference

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3. Starzl, T. E. (2008). History of clinical transplantation. In Surgery: Basic Science and Clinical Evidence: Second Edition. https://doi.org/10.1007/978-0-387-68113-9_80

4. Burke, J. F., Yannas, O. v., Quinby, W. C., Bondoc, C. C., & Jung, W. K. (1981). Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury. Annals of Surgery, 194(4). https://doi.org/10.1097/00000658-198110000-00005

5. Thomson, J. A. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391). https://doi.org/10.1126/science.282.5391.1145

6. Shamblott, M. J., Axelman, J., Wang, S., Bugg, E. M., Littlefield, J. W., Donovan, P. J., Blumenthal, P. D., Huggins, G. R., & Gearhart, J. D. (1998). Derivation of pluripotent stem cells from cultured human primordial germ cells. Proceedings of the National Academy of Sciences of the United States of America, 95(23). https://doi.org/10.1073/pnas.95.23.13726

7. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007). Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors. Cell, 131(5). https://doi.org/10.1016/j.cell.2007.11.019

8. Chen, C., Dubin, R., & Kim, M. C. (2014). Emerging trends and new developments in regenerative medicine: A scientometric update (2000-2014). In Expert Opinion on Biological Therapy (Vol. 14, Issue 9). https://doi.org/10.1517/14712598.2014.920813

9. Kolios, G., & Moodley, Y. (2013). Introduction to stem cells and regenerative medicine. In Respiration (Vol. 85, Issue 1). https://doi.org/10.1159/000345615

10. Pera, M. F., Reubinoff, B., & Trounson, A. (2000). Human embryonic stem cells. In Journal of Cell Science (Vol. 113, Issue 1). https://doi.org/10.1242/jcs.113.1.5

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