The phrase “regenerative medicine” is used so often and for so many different things, with such enthusiasm or worry, and often with a sense that this is something radically new. This paper places studies of regeneration and applications in regenerative medicine into historical perspective. In fact, the first stem cell experiment was carried out in 1907, and many important lines of research have contributed since. This paper explores both what we can learn about the history and (...) what we can learn from the history of regenerative medicine research. (shrink)

Recently, a friend of one of these writers told her story of using one of a healthcare product to activate her stem cells as part of regenerative medicine. Regenerative medicine is a field of medicine that seeks to repair or replace damaged or diseased tissues and organs. This can be done through a variety of methods, including stem cell therapy, tissue engineering, and gene therapy. This is a short review article on this rapid field called (...) regenerative medicine, in particular via a new method called photobiomodulation, especially by virtue of low-intensity laser pen treatment. Hopefully it will attract more research in this interesting direction, both for laser/photobiomodulation to boost plant growth as well as in healthcare (see also: Christianto & Smarandache, 2022; Christianto, 2023). (shrink)

From organ transplants to genetic therapies by way of the manufacture of replacement tissue, regenerative medicine incarnates a biomedical reasoning that is unique to contemporary society. As a re-engineering of the body, regenerative medicine is the most accomplished manifestation of contemporary biopolitics: it concretely announces the emergence of what sociologist Karin Knorr Cetina calls the ‘culture of life’, in which individual existence is symbolically assimilated to biological conditions. This article will examine the symbolic and ethical issues (...) of regenerative medicine, notably regarding representations of the ageing body. In doing so, it will place this new branch of biomedical research back into the context from which it emerged, with the goal of grasping the social and cultural suppositions on which regenerative medicine is based. The growing number of elderly people in Western societies is one such central element. This article therefore intends to demonstrate how regenerative medicine is rooted in the modern biomedical deconstruction of death, which underlies the contemporary technoscientific fantasy of indefinitely extending longevity. (shrink)

Novel therapies resulting from regenerative medicine and tissue engineering technology may offer new hope for patients with injuries, end-stage organ failure, degenerative disorders and many other clinical issues. Currently, patients suffering from diseased and injured organs are treated with transplanted organs. However, there is a shortage of donor organs that is worsening yearly as the population ages and new cases of organ failure increase. Scientists in the field of regenerative medicine and tissue engineering are now applying (...) the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured tissues. In addition, the stem cell field is a rapidly advancing part of regenerative medicine, and new discoveries in this field create new options for this type of therapy. For example, new types of stem cells, such as amniotic fluid and placental stem cells, that can circumvent the ethical issues associated with embryonic stem cells have been discovered. The process of somatic cell nuclear transfer and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. While stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous, adult cells have already entered the clinical setting, indicating that regenerative medicine holds much promise for the future. (shrink)

Regulation of Regenerative Medicines: A Global Perspective covers regenerative medicine regulations globally where frameworks have been or are being established. Chapters by discipline include manufacturing, supply chain, pharmacology, pharmacokinetics, toxicology, and combination product.

Reprogramming of somatic cells to a pluripotent state holds huge potentials for regenerative medicine. However, a debate over which method is better, somatic cell nuclear transfer (SCNT) or induced pluripotent stem (iPS) cells, still persists. Both approaches have the potential to generate patient‐specific pluripotent stem cells for replacement therapy. Yet, although SCNT has been successfully applied in various vertebrates, no human pluripotent stem cells have been generated by SCNT due to technical, legal and ethical difficulties. On the other (...) hand, human iPS cell lines have been reported from both healthy and diseased individuals. A recent study reported the generation of triploid human pluripotent stem cells by transferring somatic nuclei into oocytes, a variant form of SCNT. In this essay, we discuss this progress and the potentials of these two reprogramming approaches for regenerative medicine. (shrink)

The social interface between reproductive medicine and embryonic stem cell research has been investigated in a pilot study at a large IVF clinic in central China. Methods included observation, interviews with hospital personnel, and five in-depth qualitative interviews with women who underwent IVF and who were asked for their consent to the donation of embryos for use in medical (in fact human embryonic stem cell) research. This paper reports, and discusses from an ethical perspective, the results of an analysis (...) of these interviews. The participants talked of extreme social pressure to become pregnant. Once they had a baby, ‘spare’ embryos lost practical significance due to the Chinese one-child policy. In the context of decision making about donating embryos to research, the women used the clinical distinctions between ‘good and bad quality’ embryos and also between frozen and transferred embryos, as guiding moral distinctions. In the absence of concrete information about what sort of research their embryos should be used for, the women interviewed either refused consent (for fear that the embryo would be given to another couple) or accepted, expressing motives of solidarity with other women in a similar situation. This reveals that they filled the knowledge gap with an image of research improving fertility treatment. (shrink)

Experiments carried out on different tumor cell lines showed a significative growth reduction of all treated lines due to the administration of zebrafish embryo extracts withdrawn at different stem cells differentiation stages. Research conducted in order to establish which molecular events were involved in control and downregulation of cancer cell lines demonstrated a transcriptional regulation of the key cell cycle onco-supressor gene, like p53 and a post-translational modification of molecules, like pRb. Research on apoptosis and differentiation processes showed that stem (...) cells differentiating factors induce caspase-3 activation, mainly through E2F-1 gene regulation, thus hyper expressing c-Myc and activating a p73-dependent apoptotic pathway. Moreover, we demonstrated a concurrent and significative normalization of the e-cadherin/β-catenin expression, with an e-cadherin rise. Administration of SCDF in an open clinical randomized clinical trail conducted on 179 patients affected by interme... (shrink)

This paper addresses the social, cultural, and ethical dynamics of research in regenerative medicine. The author turns to both science fiction and recent developments in regenerative medicine for clues about the future of the body and medical practice, suggesting that regenerative medicine uses the body as its own resource for the purposes of preserving life, and that by attempting to remove the body from the limitations of both mortality and contingency, regenerative medicine (...) fundamentally alters the meaning of human. (shrink)

Interview made by Iñigo De Miguel, Bilbao, november 2009.

Much of the current research in regenerative medicine concentrates on stem-cell therapy that exploits the regenerative capacities of stem cells when injected into different types of human tissues. Although new therapeutic paths have been opened up by induced pluripotent cells and human mesenchymal cells, the rate of success is still low and mainly due to the difficulties of managing cell proliferation and differentiation, giving rise to non-controlled stem cell differentiation that ultimately leads to cancer. Despite being still (...) far from becoming a reality, these studies highlight the role of physical and biological constraints (e.g., cues and morphogenetic fields) placed by tissue microenvironment on stem cell fate. This asks for a clarification of the coupling of stem cells and microenvironmental factors in regenerative medicine. We argue that extracellular matrix and stem cells have a causal reciprocal and asymmetric relationship in that the 3D organization and composition of the extracellular matrix establish a spatial, temporal, and mechanical control over the fate of stem cells, which enable them to interact and control (as well as be controlled by) the cellular components and soluble factors of microenvironment. Such an account clarifies the notions of stemness and stem cell regeneration consistently with that of microenvironment. (shrink)

Technologies for enhancement of the human body historically have taken the form of an apparatus: a technological device inserted in, or appended to, the human body. The margins of these devices were clearly discernible and materially circumscribed, allowing the distinction between the corporeality of the human body and the “machine” to remain both ontologically and materially secure. This dualism has performed some important work for human rights theorists, regulators, and policy makers, enabling each to imagine they can establish where the (...) human ends and the other begins. New regenerative products such as Infuse™ and Amplify™ subsist, as animal-derived scaffolds seeded with growth hormone implanted within a prosthetic device. They are much more materially complex, and their identities thus remain open to contestation. Following Lochlann Jain’s 2006 work, I thus attend closely to their social lives, particularly the stories that are told about them and how these are employed to construct understandings of what kind of a phenomenon they are: systemic drug, biologic, or combinatorial medical device. The significance of this classificatory project is revealed in the final section of this paper, which explores how these stories shape understandings of “product failure,” liability, and causation when such products overflow their material and ontological categorization and their recipients become disturbingly “more than human.”. (shrink)

In his 1987 book "Controlling Life: Jacques Loeb and the Engineering Ideal in Biology", Philip Pauly presented his readers with the biologist Jacques Loeb and his role in developing an emphasis on control of life processes. Loeb's work on artificial parthenogenesis, for example, provided an example of bioengineering at work. This paper revisits Pauly's study of Loeb and explores the way current research in regenerative medicine reflects the same tradition. A history of regeneration research reveals patterns of thinking (...) and research methods that both echo Loeb's ideology and point the way to modern studies. Pauly's work revealed far more than we readers realized at the time of its publication. (shrink)

Various cell types cooperate to create a highly organized and dynamic micro-environmental niche in the bone marrow. Over the past several years, the field has increasingly recognized the critical roles of the interplay between bone marrow environment and hematopoietic cells in normal and deranged hematopoiesis. These advances rely on several new technologies that have allowed us to characterize the identity and roles of these niches in great detail. Here, we review the progress of the last several years, list some of (...) the outstanding questions in the field and propose ways to target the diseased environment to better treat hematologic diseases. Understanding the extrinsic regulation by the niche will help boost hematopoiesis for regenerative medicine. Based on natural development of hematologic malignancies, we propose that combinatory targeting the niche and hematopoietic intrinsic mechanisms in early stages of hematopoietic malignancies may help eliminate minimal residual disease and have the highest efficacy. The bone marrow is the home for blood-forming hematopoietic stem and progenitor cells. Normal generation of blood and immune cells depends on highly regulated interactions between these stem and progenitor cells with their surrounding environment. Emerging evidence suggests that therapeutic interventions directed at these cellular interdependencies can help boost hematopoiesis and eradicate malignant hematopoietic cells. (shrink)

This chapter brings a philosophical perspective to the concept of stem cell. Three general questions both clarify the concept of stem cell and emphasize its ambiguities: (1) How should we define stem cells? (2) What makes them different from non-stem cells? (3) What is their ontology? (i.e. what kind of property is “stemness”?) Following this last question, the Chapter distinguishes four conceptions of stem cells and highlights their respective consequences for the cancer stem cell theory. Determining what kind of property (...) stemness is, in what context, is an urgent question, at least for therapeutic strategies against cancers. I hope that this chapter also illustrates how philosophy can be useful to biology. -/- The Chapter starts by clarifying the notions of self-renewal and differentiation. This leads to the question “can we (and if so, how) distinguish stem cells from non-stem cells through these two properties?”. From that will follow an interrogation on whether stem cells belong to a natural kind. On this issue, biologists and philosophers have framed the following alternative: either the concept of stem cell refers to entities (the cells that belong to the stem cell natural kind) or it refers to a transient and reversible cell state. I will argue that four conceptions of stemness should be distinguished rather than two. Finally, I will develop the case of the cancer stem cell (CSC) theory in order to show why it is crucial to answer the ontological question: some therapies might or might not be efficient depending on what stemness is. (shrink)

The history and context of the public policy regarding stem cell research in the European Union are complex. The regulations respond to and aim to realize political and economic goals across a large region that is culturally diverse, as well as addressing moral judgments on a contested emerging area of research. This history and context are relevant for the arguments developed here in relation to autologous stem cell research and how it is affected by those regulations.The EU is currently an (...) open market across 28 countries with different languages as well as varied cultural, religious, and political histories. Bridging the diverse traditions and their corresponding local policies and regulations is often a... (shrink)

Alexis Carrel’s and Keith Porter’s accomplishments at the Rockefeller Institute for Medical Research, 1910–1950, were fundamental to the creation of the field of tissue culture.

Regenerative Medicine promises to develop treatments to regrow healthy tissues and cure the physical body. One of the emerging developments within this field is regenerative implants, such as jawbone or heart valve implants, that can be broken down by the body and are gradually replaced with living tissue. Yet challenges for embodiment are to be expected, given that the implants are designed to integrate deeply into the tissue of the living body, so that implant and body become (...) one. In this paper, we explore how regenerative implants may affect the embodied experience of implant recipients. To this end, we take a phenomenological approach. First, we explore what insights the existing phenomenological and empirical literature on embodiment offers regarding the experience of illness and of living with regular (non-regenerative) implants and organ transplants. Second, we apply these insights to better understand how future implant recipients might experience living with regenerative implants. Third, we conclude that concepts and considerations from the existing phenomenological literature do not sufficiently address what it might be like to live with an implantable technology that, over time, becomes one with the living body. We argue that the interwovenness and intimate relationship of people living with regenerative implants should be understood in terms of ‘entanglement’. Entanglement allows us to explore the complexities of human-technology relations, acknowledging the inseparability of humans and implantable technologies. Our theoretical foundations regarding the role of embodiment may be tested empirically once more people will be living with regenerative implants. (shrink)

The identification and valorization of unacknowledged, feminized forms of economic productivity has been an important task for feminist theory. In this article, we expand and rethink existing definitions of labour, in order to recognize the essential economic role women play in the stem cell and regenerative medicine industries, new fields of biomedical research that are rapidly expanding throughout the world. Women constitute the primary tissue donors in the new stem cell industries, which require high volumes of human embryos, (...) oöcytes, foetal tissue and umbilical cord blood. Such material is generally given for free in the advanced industrial democracies, constituted as a surplus (‘spare’ embryos) or waste (umbilical cord ‘afterbirth’, cadaveric foetuses, poor quality oöcytes) whose generative powers should not be withheld from others. At the same time, among impoverished female populations in developing nations, such biological material is now often procured through frankly transactional relations, where women undertake risky procedures for small fees. In each case, female bodily productivity is mobilized to support bioeconomic research, yet the economic value involved in these relations is largely unacknowledged. In this article, we consider both the gift economy and the transactional economy for reproductive tissues as a form of labour. In order to fully conceptualize the specificities of feminized productivity in the bioeconomy, we distinguish between earlier feminist theories of reproductive labour and the emerging practices generated by stem cell research, which we term regenerative labour. We consider how historical transformations in the regulation of feminized labour and the technical repertoires of stem cell research renegotiate the productivity limits of female reproductive biology, opening it out to novel and profitable forms of surplus value and enrolling women in complex negotiations over their role in bioeconomic activity. (shrink)

Evolution exploits the physics of non‐neural bioelectricity to implement anatomical homeostasis: a process in which embryonic patterning, remodeling, and regeneration achieve invariant anatomical outcomes despite external interventions. Linear “developmental pathways” are often inadequate explanations for dynamic large‐scale pattern regulation, even when they accurately capture relationships between molecular components. Biophysical and computational aspects of collective cell activity toward a target morphology reveal interesting aspects of causation in biology. This is critical not only for unraveling evolutionary and developmental events, but also for (...) the design of effective strategies for biomedical intervention. Bioelectrical controls of growth and form, including stochastic behavior in such circuits, highlight the need for the formulation of nuanced views of pathways, drivers of system‐level outcomes, and modularity, borrowing from concepts in related disciplines such as cybernetics, control theory, computational neuroscience, and information theory. This approach has numerous practical implications for basic research and for applications in regenerative medicine and synthetic bioengineering. (shrink)

What is now familiarly referred to as the ‘embryonic stem (ES) cell’ is a recent biological category whose origins lie in research into benign and malignant teratomas carried out in the 1950s, 60s and 70s. In these studies, the question of the normal or pathological character of the ES cell was a matter of considerable debate and indeed the term ES cell was often used interchangeably with that of the embryonal carcinoma (EC) cell. This article argues that the indecisiveness of (...) the entity known as the ES cell—its refusal to commit to established demarcations between the normal and the pathological—continues to haunt the field of stem cell science. Exploring the prehistory of research into ES cells, early theories of cancer (in particular the embryonal theory expounded by Julius Cohnheim) and recent theoretical critiques of the somatic mutation theory, the article not only points to a shift in understandings of the normal and the pathological but asks under what conditions such shifts are able to take place. (shrink)

It may soon become possible not just to replace, but to re-grow healthy tissues after injury or disease, because of innovations in the field of Regenerative Medicine. One particularly promising innovation is a regenerative valve implant to treat people with heart valve disease. These implants are fabricated from so-called ‘smart’, ‘lifelike’ materials. Implanted inside a heart, these implants stimulate re-growth of a healthy, living heart valve. While the technological development advances, the ethical implications of this new technology (...) are still unclear and a clear conceptual understanding of the notions ‘smart' and ‘lifelike' is currently lacking. In this paper, we explore the conceptual and ethical implications of the development of smart lifelike materials for the design of regenerative implants, by analysing heart valve implants as a showcase. In our conceptual analysis, we show that the materials are considered ‘smart’ because they can communicate with human tissues, and ‘lifelike’ because they are structurally similar to these tissues. This shows that regenerative valve implants become intimately integrated in the living tissues of the human body. As such, they manifest the ontological entanglement of body and technology. In our ethical analysis, we argue this is ethically significant in at least two ways: It exacerbates the irreversibility of the implantation procedure, and it might affect the embodied experience of the implant recipient. With our conceptual and ethical analysis, we aim to contribute to responsible development of smart lifelike materials and regenerative implants. (shrink)