Regenerative Medicine

Abstract

Regenerative medicine is a distinct major advancement in medical treatment which is based on the principles of stem cell technology and tissue engineering in order to replace or regenerate human tissues and organs and restore their functions. After many years of basic research, this approach is beginning to represent a valuable treatment option for acute injuries, chronic diseases and congenital malformations. Nevertheless, it is a little known field of research. The purpose of this review is to convey the state of the art in regenerative medicine in terms of historical steps, used strategies and pressing problems to solve in the future. This review represents a good starting point for more in-depth studies and personal research projects.

Keywords

Introduction

Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs.

Regenerative medicine also includes the possibility of growing tissues and organs in the laboratory and implanting them when the body cannot heal itself. When the cell source for a regenerated organ is derived from the patient's own tissue or cells, the challenge of organ transplant rejection via immunological mismatch is circumvented. This approach could alleviate the problem of the shortage of organs available for donation.

Some of the biomedical approaches within the field of regenerative medicine may involve the use of stem cells.

Examples include the injection of stem cells or progenitor cells obtained through directed differentiation (cell therapies); the induction of regeneration by biologically active molecules administered alone or as a secretion by infused cells (immunomodulation therapy); and transplantation of in vitro grown organs and tissues (tissue engineering (1)

Fundamental Principles of Regenerative Medicine

The 5 Basic Principles of Regenerative Medicine

1. Regenerating Lost or Damaged Tissue

Regenerative medicine’s ultimate goal is found in its name: to heal by regenerating lost or damaged tissue. We can use osteoarthritis as a good example. Osteoarthritis is a degenerative disease caused by the gradual breakdown of cartilage. As the amount of cartilage between the two bones of a given joint deteriorates, the bones have more opportunity to grind on each other. It is this that causes osteoarthritis pain.

Stem cell and platelet-rich plasma (PRP) injections are designed to stimulate the growth of new cartilage. As cartilage is restored, pain decreases and function improves.

2. Tissue and Organ Growth          

While regenerative medicine at the consumer level focuses on addressing lost or damaged tissue, there are wider efforts to perfect the science for the purposes of growing organs and tissue in a lab environment. Indeed, there are biomedical companies already working on this, and, although they have not perfected their processes yet, they are well on their way. The goal is to be able to produce tissue and organs that could eventually supplement or completely replace donated organs and tissue.

3. Promoting Natural Healing

Regenerative medicine is rooted in the understanding that the human body is designed to heal itself. It doesn’t always do that, but the potential is there. Regenerative medicine seeks to tap into that potential. It seeks to give the body the help it needs to naturally heal itself. Where it succeeds, there is less of a need for surgeries, pharmacological treatments, and fabricated medical devices.(2)

4. Stem Cells and PRP Are the Starting Point

All regenerative therapies are rooted in either human stem cells or PRP. Some utilize both. If you are being treated for osteoarthritis, your doctor might recommend injections of one or the other. The important thing to note is that you would donate your own stem cells or blood plasma. This all but eliminates the risk of complications and rejection. For the record, current FDA regulations allow for regenerative therapies as long as the biological material is autologous (meaning it has been donated by the patient being treated) and minimally manipulated. We make this point only to counter false claims that regenerative medicine is an unregulated Wild West scenario. It is anything but.

5. A More Natural Type of Medicine

Regenerative medicine is a more natural type of medicine in that it seeks to use what the body already has available to promote healing. Unlike invasive surgical procedures, outpatient regenerative medicine therapies are minimally invasive. When the therapies perform as expected, they reduce the need for prescription medications.(3)

Stem Cells and Their Therapeutic Potential

Stem cells are a form of undifferentiated cell that has the potential to proliferate (self-renew), emerge from a single cell (clonal), and develop into different types of cells and tissues (potent). There are several sources of stem cells of varied potency.

Although stem cell research has grown at an exponential rate, medicinal applications have moved considerably more slowly. The study is currently focused on understanding embryonic, adult, and inducible pluripotent stem cells. Adult stem cell research translation has demonstrated a decisive benefit that is larger than the present standard of care in the field of cardiovascular medicine. The future of stem cell research and therapy will continue to open up new diagnostic, therapeutic, and tissue regeneration pathways.(4)

In cellular treatment, stem cells can be employed to repair damaged cells or rebuild tissues. Furthermore, stem cells have advanced our understanding of development as well as disease causation. Cell lines that are particular to a disease can also be grown and employed in medication research .

Despite considerable improvements in stem cell biology, ethical concerns about embryonic stem cells, tumour growth, and rejection restrict their applicability. However, several of these constraints are being overcome, which might lead to significant advancements in illness management. This article provides an introduction to the world of stem cells, including its definition, origin, and categorization, as well as their uses in regenerative medicine.(5)

Advances In Tissue   Engineering and Organ Regeneration

Tissue engineering, which is now being categorized as a form of regenerative medicine, can be defined as biomedical engineering to reconstruct, repair, and improve biological tissues. Research efforts in tissue engineering have been ongoing and it is emerging as one of the key areas of medical research. Furthermore, there are vast developments in tissue engineering, which involve leveraging of technologies from biomaterials, molecular medicine, biochemistry, nanotechnology, genetic and biomedical engineering for regeneration and cell expansion targets to restructure and/or repair human organs.(6)

Gene Therapies for Regenerative Medicine

Gene therapy is a very promising and attractive technology that involves the in vitro or in vivo introduction of exogenous genes into cells for biological and therapeutic purposes. Regardless of the final goal for experimental biology and gene therapy, the first key task is to enable the gene to internalise into the cell as efficiently as possible and to facilitate the expression for a long or short time period.

Gene therapy technologies have been used for different methods of viral vectors, non-viral vectors, and physical technologies to deliver genetic materials to cells and tissues. Regenerative medicine is an interdisciplinary field that combines engineering and live sciences to develop techniques that enable the restoration, maintenance, or enhancement of living tissues and organs on biomaterials.

Its fundamental aim is the creation of natural tissue with the ability to restore missing organs or tissue functions that the organism has not been able to regenerate in physiological conditions. In planning gene therapy strategies for regenerative medicine therapy, one must consider two major avenues: direct gene delivery in vivo using viral or non-viral vectors or in vitro cell-mediated gene therapy. In both cases, the aim is to deliver a therapeutic gene of a growth factor or cytokine into the target tissue. Gene therapy is a preferred technology over the addition of a growth factor to the cell as, typically: (7) 

The half-life of the selected growth factor is short; (8) a single administration is usually not sufficient to elicit a biological effect; (9) the quantities required are prohibitively expensive; and,  continuous protein production increases the likelihood that a desired outcome will be achieved. This review summarises regenerative medicine therapy based on gene therapy and suggests new areas of investigation that may help to resolve problems. There is a remarkable overlap in how scientists and researchers employ the terms “tissue engineering” and “regenerative medicine,” and thus, we use these terms together in this review as regenerative medicine.

Case Studies

Regenerative medicine as a field is quite broad but is generally understood to focus on the regeneration, repair, and replacement of cells, tissues, and organs to restore function (Mason and Dunnill, 2008). The aspect of regenerative medicine on which this case study focuses relates to the ability to treat—or cure—genetic hematologic disease safely and effectively, and the significant trade-offs that come with these novel therapies.

The story of this therapy begins in the history of bone marrow transplants. The medicinal value of bone marrow has long been recognized and was first discussed in the 1890s as a potential treatment (administered orally) of “diseases believed to be characterized by defective hemogenesis” (Quine, 1896).

While allogeneic bone marrow transplant (in which stem cells from a donor are collected and transplanted into the recipient) may be the most broadly known form of hematopoietic stem and progenitor cell (HSPC) transplant, a range of other cell types are also used. HSPCs used in transplant can be either allogeneic (i.e., from a donor) or autologous (i.e., from the person who will also receive the transplant). The cells used in transplant research and clinical care can come from bone marrow, peripheral blood stem cells (PBSCs), umbilical cord blood, and pluripotent stem cell-derived cells.

A major challenge throughout the history of HSPC transplantation has been the dire risks associated with these transplants, including the morbidity and mortality caused by immunological reactions between the transplanted cells and the tissues of the recipient. In particular, graft-versus-host disease (GVHD) is a serious response in which the transplanted stem cells view the recipient’s tissues as foreign and mount an immune response, attacking the recipient’s body. If an autologous transplant is not possible given the nature of the disease to be treated, an immunologically well-matched healthy donor for allogeneic transplant is critical. For genetic hematologic disease, a new approach that would not only treat but cure the condition is now being tested: genetic modification of the patient’s own HSPCs to correct or compensate for the defect, followed by transplantation of the corrected autologous cells.

This challenge of matching transplantable cells to patients has driven evolution within the field of regenerative medicine, including logistical fixes in the form of HSPC registries and banks to technological approaches including the use of pluripotent stem cell-derived cell sources and genome editing (e.g., clustered regularly interspaced short palindromic repeats [CRISPR]).

This challenge of immunological matching has also driven significant ethical challenges, even beyond the substantial risks of HSPC transplantation itself. In contrast to many novel technologies, where finances are a primary barrier to access, in the case of regenerative medicine, there is the additional barrier of  biology European descent. Furthermore, genetic hematologic diseases like sickle cell disease (SCD) and thalassemia, for which HSPC transplant is the only established cure (and a fraught one, at that), have struggled to garner the financial and grant support needed to move research forward. This challenge persists despite SCD being three times more prevalent in the United States than cystic fibrosis, which has historically benefited from generous public and private funding (Farooq et al., 2020; Wailoo and Pemberton, 2006). All of this stands on a background of long-understood barriers even to standard of care (e.g., adequate pain management) for individuals with SCD in particular (Haywood et al., 2009). Together, these facts raise concerns related to equity and access at multiple stages of research, development, and clinical care.

Finally, advances in this science have also attracted the attention of those who are willing to take advantage of patients under the guise of cutting-edge therapy, creating a robust market of direct-to-consumer (DTC) cell-based services and interventions that at best waste time and money and at worst cause serious harm or death (Bauer et al., 2018).

Challenges And Ethical Considerations

The newly recognized multi-disciplinary field of regenerative medicine aims at the replacement, repair or restoration of normal function to disease organs/tissues by the delivery of safe, effective and consistent therapies composed of living cells, administered either alone or in combination with specially designed materials (Langer & Vacanti 1993).

The concept of tissue regeneration is by no means new—going back a long time as illustrated by the famous legend of Prometheus. Prometheus was a champion of human equality. He stole fire from Zeus, which he then gave to the mortals. As a punishment for his crime, Zeus bound him to a rock and sent a giant eagle to eat his liver. However, his liver re-grew every night and the eagle had to return again and again.

Tissue regeneration is also a primitive event, occurring in many organisms such as newts where it is well known that a sectioned limb will be completely regenerated after a six to eight-week period.

In humans, regenerative medicine such as solid organ transplantation and cell therapy have been practised for many years, for example, kidney transplantation was first performed in 1954 (Murray & Holden 1954) and bone marrow transplantation since 1968 (for review see Appelbaum 2007).

The field covers what was thought originally to be separate therapeutic areas: cell therapy and tissue engineering (creation of in vitro tissues/organs for subsequent transplantation as fully functioning organs or as tissue patches) among others (Baron & Storb 2008). Therapeutic examples include replacement (transplantation), repair (exogenous cell therapy) or regeneration (mobilization of endogenous pools of stem cells).

CONCLUSION

Regenerative medicine represents a transformative frontier in healthcare, offering the potential to repair, replace, or regenerate damaged tissues and organs. By harnessing the power of stem cells, tissue engineering, gene editing, and advanced biomaterials, it moves beyond conventional treatments that only manage symptoms. Clinical successes in bone marrow transplantation, engineered skin grafts, and emerging therapies for cardiovascular, neurological, and ocular diseases highlight its promise.(19)

However, challenges remain, including safety concerns, regulatory hurdles, ethical debates, and the need for cost-effective scalability. Addressing these issues will be critical to ensure that regenerative therapies are safe, accessible, and ethically responsible.

Looking ahead, the integration of stem cell biology, genomics, biomaterials, and artificial intelligence is likely to expand the scope of regenerative medicine even further. Ultimately, it has the potential not only to extend life but also to restore quality of life, shifting modern medicine from disease management to true biological repair and healing.(20)

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