Lancet Commission: Stem cells and regenerative medicine

Published on Oct 1, 2017in The Lancet 53.25
· DOI :10.1016/S0140-6736(17)31366-1
Giulio Cossu68
Estimated H-index: 68
(Manchester Academic Health Science Centre),
Martin A. Birchall33
Estimated H-index: 33
(University College London)
+ 16 AuthorsJames F. Wilson89
Estimated H-index: 89
(University College London)
Abstract
In this Commission, we argue that a combination of poor quality science, unclear funding models, unrealistic hopes, and unscrupulous private clinics threatens regenerative medicine's social licence to operate. If regenerative medicine is to shift from mostly small-scale bespoke experimental interventions into routine clinical practice, substantial rethinking of the social contract that supports such research and clinical practice in the public arena will be required. For decades, stem cell therapy was predominantly limited to bone marrow transplantation for haematological diseases and epidermis transplantation for large burns. Tissue engineering and gene therapy faced huge challenges on their way to clinical translation—a situation that began to change only at the end of the 1990s. The past 10 years have seen an exponential growth in experimental therapies, broadly defined as regenerative medicine, entering the clinical arena. Results vary from unequivocal clinical efficacy for previously incurable and devastating diseases to (more frequently) a modest or null effect. The reasons for these widely different outcomes are starting to emerge. At this stage in their evolution, these experimental therapies (which include, but are not limited to, cell and gene therapy, tissue engineering, and new generation drugs) are necessarily financially expensive. Rigorous and costly clinical-grade procedures have to be followed in the development of medicinal products (involving cells, genetically manipulated cells, viral vectors, or biomaterials with or without cells), often produced in a very limited run. The cost of developing sufficiently high-quality trials means that only wealthier countries are able to fund them. Although public investments in this field are massive internationally, they do not carry guaranteed commercial returns. Compared with conventional drug development, such products follow a highly uncertain route to market. Furthermore, new therapies expose patients to risks, some of which are difficult to predict even with inbuilt safeguards. Despite the relatively small number of clinical successes, optimism and excitement about the potential effect or implications of this field remain great. This enthusiasm has led to gaps between people's expectations that new therapies should be available, often inflated by media reports, and the realities of translating regenerative technologies into clinical practice. The same environment is also permissive of one-off compassionate applications and poorly regulated trials. Indeed, the number of poorly regulated clinics has grown; clinics that appeal to desperate patients and their families, who, in the absence of reliable clinical knowledge from trials, cannot be adequately informed to assess the risks and benefits. These ethical and governance issues pose a challenge to scientists in engaging with the public, the press, and decision-making bodies in different national health systems. Political agendas might not coincide with the public good. In poorly regulated states, the authorisation of a novel therapy might be politically attractive, even when efficacy is unconfirmed, and the cost to taxpayers means other patients are deprived of established and effective therapies. These challenges are difficult to address and solve. We recommend a solution that lies in a coordinated strategy with four pillars: better science, better funding models, better governance, and better public and patient engagement.
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  • Citations (19)
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References161
Published on May 1, 2015in Stem Cell Research 3.90
Achim Rosemann7
Estimated H-index: 7
Highlights • The paper tackles the organizational challenges of international stem cell trials • It explores the obstacles that result from regulatory variation across countries • The article argues for the formation of an international support structure • Such a structure will be of use to academic and corporate trial sponsors • Five steps through which such a support structure could be realized are introduced
2 Citations Source Cite
Published on Jan 1, 1990in Advances in Experimental Medicine and Biology 1.76
Jerry R. Mendell81
Estimated H-index: 81
(Ohio State University)
The issue of immunosuppressive therapy in relation to myoblast transfer is extremely important. Several points must be addressed. The first to consider is whether immunosuppression is necessary for this treatment to be successful. The second is the choice of drugs to be used and what impact they will have on the natural history of the disease exclusive of the potential benefits of the transplanted cells.
5 Citations Source Cite
Published on May 22, 2013
Ruha Benjamin1
Estimated H-index: 1
Stem cell research has sparked controversy and heated debate since the first human stem cell line was derived in 1998. Too frequently these debates devolve to simple judgments-good or bad, life-saving medicine or bioethical nightmare, symbol of human ingenuity or our fall from grace-ignoring the people affected. With this book, Ruha Benjamin moves the terms of debate to focus on the shifting relationship between science and society, on the people who benefit-or don't-from regenerative medicine a...
21 Citations
Published on Jul 1, 2015in Nature Chemical Biology 13.84
James Palacino17
Estimated H-index: 17
,
Susanne E Swalley3
Estimated H-index: 3
+ 37 AuthorsCaroline Gubser Keller2
Estimated H-index: 2
A high-throughput screen identified a small molecule that promoted inclusion of SMN2 exon 7, increased SMN2 protein levels and extended survival in a SMA mouse model through stabilization of the interaction between SMN2 pre-mRNA and U1 snRNP complex.
112 Citations Source Cite
Published on Jan 1, 1999in Seminars in Hematology 3.93
E D Thomas1
Estimated H-index: 1
129 Citations
Published on Jan 20, 2014in Human Gene Therapy 4.24
Ronald G. Crystal133
Estimated H-index: 133
62 Citations Source Cite
Published on Jan 1, 1997
Marjorie B. Zucker2
Estimated H-index: 2
,
Howard D. Zucker2
Estimated H-index: 2
,
Alexander Morgan Capron21
Estimated H-index: 21
Preface Foreword Alexander Morgan Capron Contributors 1. Medical futility: a useful concept? Howard Brody 2. Death with dignity Patricia Brophy 3. Physicians and medical futility: experience in the critical care setting Harry S. Rafkin and Thomas Rainey 4. Physicians and medical futility: experience in the setting of general medical care Norton Spritz 5. Futility issues in pediatrics Joel E. Frader and Jon Watchko 6. Medical futility: a nusing home perspective Ellen Knapik Bartoldus 7. Alternati...
23 Citations Source Cite
Published on May 1, 2001in Nature Reviews Neuroscience 32.63
Stephen B. Dunnett88
Estimated H-index: 88
(Cardiff University),
Anders Björklund147
Estimated H-index: 147
(Cardiff University),
Olle Lindvall105
Estimated H-index: 105
(Cardiff University)
about whether but also about how grafts exert their functional effects, it becomes apparent that effective therapies can only be developed hand-in-hand with acquiring a rational understanding of the neurobiological principles that underlie the integration and function of grafted cells in the damaged nervous system. Successful transplantation of catecholamine-secreting cells in the nervous system was first achieved by Olson and colleagues in the early 1970s by grafting adrenal chromaffin cells or...
217 Citations Source Cite
Published on Jul 1, 2015in Cell Stem Cell 23.29
Alan Trounson83
Estimated H-index: 83
(Hudson Institute),
Courtney McDonald14
Estimated H-index: 14
(Hudson Institute)
Clinical investigations using stem cell products in regenerative medicine are addressing a wide spectrum of conditions using a variety of stem cell types. To date, there have been few reports of safety issues arising from autologous or allogeneic transplants. Many cells administered show transient presence for a few days with trophic influences on immune or inflammatory responses. Limbal stem cells have been registered as a product for eye burns in Europe and mesenchymal stem cells have been app...
330 Citations Source Cite
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Cited By19
Published on Feb 1, 2018in Expert Opinion on Biological Therapy 3.97
Christian Morsczeck16
Estimated H-index: 16
(University of Regensburg),
Torsten E. Reichert34
Estimated H-index: 34
(University of Regensburg)
ABSTRACTIntroduction: Human dental stem cells can be obtained from postnatal teeth, extracted wisdom teeth or exfoliated deciduous teeth. Due to their differentiation potential, these mesenchymal stem cells are promising for tooth repair. Therefore, the development of dental tissue regeneration represents a suitable but challenging, target for dental stem cell therapies.Areas covered: In this review, the authors provide an overview of human dental stem cells and their properties for regeneration...
1 Citations Source Cite
Published on Jan 1, 2018in Biochemical Pharmacology 4.24
Jeannette M. Osterloh5
Estimated H-index: 5
(Gladstone Institutes),
Kevin Mullane11
Estimated H-index: 11
(Gladstone Institutes)
Abstract Biomedical research is being transformed by the discovery and use of human pluripotent stem cells (hPSCs). Remarkable progress has been made, and assorted clinical trials are underway related to the application of stem cell therapy, including transplantation of hPSC-derived cells, in situ reprogramming or transdifferentiation, and utilization of targets and compounds identified from patient-derived stem cells. However, the pace of discovery is overwhelming efforts to replicate the work ...
4 Citations Source Cite
Published on Jan 1, 2018in Experimental Gerontology 3.22
Jagadish K. Chhetri5
Estimated H-index: 5
,
Philipe de Souto Barreto9
Estimated H-index: 9
+ 3 AuthorsMatteo Cesari55
Estimated H-index: 55
(University of Toulouse)
Abstract Sarcopenia is characterized by reduced skeletal muscle mass and strength in older individuals. It is one of the leading cause of physical limitation in older adults, and associated with wide spectrum of adverse events including disability and mortality. The phenomenon of chronic-inflammation or inflamm-aging with aging is known to be a major contributor to myriad of geriatric conditions including sarcopenia. Recent advances in regenerative medicine, in particular cell therapy have opene...
6 Citations Source Cite
Published on Apr 1, 2018in Journal of Dental Research 5.38
William V. Giannobile63
Estimated H-index: 63
,
Yang Chai46
Estimated H-index: 46
(University of Southern California)
+ 11 AuthorsC. S. Sfeir (University of Pittsburgh)
Author(s): Giannobile, WV; Chai, Y; Chen, Y; Healy, KE; Klein, O; Lane, N; Longaker, MT; Lotz, JC; Mooney, DJ; Sfeir, CS; Urata, M; Wagner, WR; Wu, BM; Kohn, DH
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Published on Apr 1, 2018in The Journal of Urology 5.38
Guido Barbagli37
Estimated H-index: 37
,
Ilgar Akbarov1
Estimated H-index: 1
(University of Cologne)
+ 9 AuthorsUdo Rebmann4
Estimated H-index: 4
Purpose: We investigated whether tissue engineered material may be adopted using standard techniques for anterior urethroplasty.Materials and Methods: We performed a retrospective multicenter study in patients with recurrent strictures, excluding those with failed hypospadias, lichen sclerosus, traumatic and posterior strictures. A 0.5 cm2 oral mucosa biopsy was taken from the patient cheek and sent to the laboratory to manufacture the graft. After 3 weeks the tissue engineered oral mucosal Muko...
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Published on Apr 1, 2018in Transfusion and Apheresis Science 1.75
Erden Atilla6
Estimated H-index: 6
(Ankara University),
Pelin Kılıç1
Estimated H-index: 1
(Ankara University),
Gunhan Gurman14
Estimated H-index: 14
(Ankara University)
Abstract Tremendous effort and knowledge have elucidated a new era of ‘cellular therapy,’ also called “live” or “living” drugs. There are currently thousands of active clinical trials that are ongoing, seeking hope for incurable conditions thanks to the increased accessibility and reliability of gene editing and cellular reprogramming. Accomplishments in various adoptive T cell immunotherapies and chimeric antigen receptor (CART) T cell therapies oriented researchers to the field. Cellular thera...
3 Citations Source Cite
Af Pellegata3
Estimated H-index: 3
(University College London),
Alfonso M. Tedeschi1
Estimated H-index: 1
(University College London),
P De Coppi53
Estimated H-index: 53
(University College London)
Tissue engineering aims to regenerate and recapitulate a tissue or organ that has lost its function. So far successful clinical translation has been limited to hollow organs in which rudimental vascularization can be achieved by inserting the graft into flaps of the omentum or muscle fascia. This technique used to stimulate vascularization of the graft takes advantage of angiogenesis from existing vascular networks. Vascularization of the engineered graft is a fundamental requirement in the proc...
4 Citations Source Cite
Published on Oct 1, 2018in Current Opinion in Cell Biology 10.02
Shiqi Hu (University of North Carolina at Chapel Hill), Brenda M. Ogle20
Estimated H-index: 20
(University of Minnesota),
Ke Cheng30
Estimated H-index: 30
(University of North Carolina at Chapel Hill)
It is estimated that 18 Americans die every day waiting for an organ donation. And even if a patient receives the organ that s/he needs, there is still >10% chance that the new organ will not work. The field of tissue engineering and regenerative medicine aims to actively use a patient's own cells, plus biomaterials and factors, to grow specific tissues for replacement or to restore normal functions of that organ, which would eliminate the need for donors and the risk of alloimmune rejection. In...
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Published on May 1, 2018in Nature 41.58
James M. Wells32
Estimated H-index: 32
(Cincinnati Children's Hospital Medical Center),
F. Watt101
Estimated H-index: 101
(King's College London)
Mammalian organs comprise an extraordinary diversity of cell and tissue types. Regenerative organs, such as the skin and gastrointestinal tract, use resident stem cells to maintain tissue function. Organs with a lower cellular turnover, such as the liver and lungs, mostly rely on proliferation of committed progenitor cells. In many organs, injury reveals the plasticity of both resident stem cells and differentiated cells. The ability of resident cells to maintain and repair organs diminishes wit...
7 Citations Source Cite
Published on May 29, 2018in Frontiers in Cardiovascular Medicine
Carlijn Carlijn Bouten45
Estimated H-index: 45
,
Anthal I.P.M. Smits3
Estimated H-index: 3
,
Frank P. T. Baaijens1
Estimated H-index: 1
In situ heart valve tissue engineering using cell-free synthetic, biodegradable scaffolds is under development as a clinically attractive approach to create living valves right inside the heart of a patient. In this approach, a valve-shaped porous scaffold "implant" is rapidly populated by endogenous cells that initiate neo-tissue formation in pace with scaffold degradation. While this may constitute a cost-effective procedure, compatible with regulatory and clinical standards worldwide, the new...
1 Citations Source Cite