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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 Cossu69
Estimated H-index: 69
(Manchester Academic Health Science Centre),
Martin A. Birchall35
Estimated H-index: 35
(University College London)
+ 16 AuthorsJames F. Wilson93
Estimated H-index: 93
(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.
  • References (161)
  • Citations (23)
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References161
Newest
Published on Aug 1, 2017in Nature 41.58
Hong Ma27
Estimated H-index: 27
(Oregon National Primate Research Center),
Nuria Marti-Gutierrez1
Estimated H-index: 1
(Oregon Health & Science University)
+ 28 AuthorsRiffat Ahmed10
Estimated H-index: 10
(Oregon Health & Science University)
CRISPR–Cas9 genome editing is used to induce a DNA repair response and correct a disease-causing heterozygous mutation in human embryos with reduced mosaicism and preferential repair using the wild-type copy of the gene.
259 Citations Source Cite
Published on Jun 1, 2017in Embo Molecular Medicine 10.29
Alessandro Aiuti48
Estimated H-index: 48
(Vita-Salute San Raffaele University),
M.G. Roncarolo85
Estimated H-index: 85
(Vita-Salute San Raffaele University),
Luigi Naldini92
Estimated H-index: 92
(Vita-Salute San Raffaele University)
Gene and cell therapy research recently reached a fundamental milestone toward the goal to deliver new medicines for orphan diseases. In 2016, the European Commission granted market approval to GlaxoSmithKline (GSK) for ex vivo hematopoietic stem cell (HSC) gene therapy for the treatment of adenosine deaminase (ADA)‐deficient severe combined immunodeficiency (SCID), a very rare congenital disorder of the immune system. The new medicine, named Strimvelis™, is an advanced therapy medicinal product...
43 Citations Source Cite
Published on Dec 13, 2016in JAMA 47.66
Aaron S. Kesselheim40
Estimated H-index: 40
(Brigham and Women's Hospital),
Jerry Avorn110
Estimated H-index: 110
(Brigham and Women's Hospital)
38 Citations Source Cite
Published on Dec 1, 2016in Embo Molecular Medicine 10.29
Giulio Cossu69
Estimated H-index: 69
(University of Manchester),
Stefano C. Previtali35
Estimated H-index: 35
+ 30 AuthorsMarina Scarlato21
Estimated H-index: 21
Abstract Intra‐arterial transplantation of mesoangioblasts proved safe and partially efficacious in preclinical models of muscular dystrophy. We now report the first‐in‐human, exploratory, non‐randomized open‐label phase I–IIa clinical trial of intra‐arterial HLA‐matched donor cell transplantation in 5 Duchenne patients. We administered escalating doses of donor‐derived mesoangioblasts in limb arteries under immunosuppressive therapy (tacrolimus). Four consecutive infusions were performed at 2‐m...
55 Citations Source Cite
Published on Sep 14, 2016in Nature 41.58
Alison Abbott Aa32
Estimated H-index: 32
2 Citations Source Cite
Published on Jul 1, 2016in Nature Biotechnology 35.72
Eric Smalley3
Estimated H-index: 3
3 Citations Source Cite
Published on Jul 1, 2016in The Lancet 53.25
Maria Sessa22
Estimated H-index: 22
,
Laura Lorioli6
Estimated H-index: 6
+ 26 AuthorsAndrea Calabria13
Estimated H-index: 13
Summary Background Metachromatic leukodystrophy (a deficiency of arylsulfatase A [ARSA]) is a fatal demyelinating lysosomal disease with no approved treatment. We aimed to assess the long-term outcomes in a cohort of patients with early-onset metachromatic leukodystrophy who underwent haemopoietic stem-cell gene therapy (HSC-GT). Methods This is an ad-hoc analysis of data from an ongoing, non-randomised, open-label, single-arm phase 1/2 trial, in which we enrolled patients with a molecular and b...
105 Citations Source Cite
Published on Jul 1, 2016in Gene Therapy 3.20
Xue Hy1
Estimated H-index: 1
,
Zhang X1
Estimated H-index: 1
+ 3 AuthorsXu Y1
Estimated H-index: 1
Clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9 (CRISPR-Cas9) is a genome editing tool derived from microbial adaptive immune defense system.1 The nuclease Cas9 can generate double-strand breaks (DSBs) on the target DNA sequences in a site-specific way directed by a singly guide RNA (sgRNA) upon the existence of an pro-tospacer adjacent motif (PAM) sequence (Figure 1a).2, 3, 4 The resultant DSDs are repaired by either non-homologous end-joining (NHEJ) or ho...
14 Citations Source Cite
Published on Jun 1, 2016in Stem cell reports 6.54
George Q. Daley106
Estimated H-index: 106
(Harvard University),
Insoo Hyun18
Estimated H-index: 18
(Case Western Reserve University)
+ 22 AuthorsJoyce Frey-Vasconcells2
Estimated H-index: 2
The International Society for Stem Cell Research (ISSCR) presents its 2016 Guidelines for Stem Cell Research and Clinical Translation (ISSCR, 2016). The 2016 guidelines reflect the revision and extension of two past sets of guidelines (ISSCR, 2006; ISSCR, 2008) to address new and emerging areas of stem cell discovery and application and evolving ethical, social, and policy challenges. These guidelines provide an integrated set of principles and best practices to drive progress in basic, translat...
71 Citations Source Cite
Cited By23
Newest
Published on Jun 6, 2019in Cell Stem Cell 23.29
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Published on May 2, 2019in Stem Cells International 3.99
Mimmi Patrikoski (University of Helsinki), Bettina Mannerström9
Estimated H-index: 9
(University of Helsinki),
Susanna Miettinen31
Estimated H-index: 31
Adipose stromal/stem cells (ASCs) are an ideal cell type for regenerative medicine applications, as they can easily be harvested from adipose tissue in large quantities. ASCs have excellent proliferation, differentiation, and immunoregulatory capacities that have been demonstrated in numerous studies. Great interest and investment have been placed in efforts to exploit the allogeneic use and immunomodulatory and anti-inflammatory effects of ASCs. However, bridging the gap between in vitro and in...
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Published on May 1, 2019in Science Advances
Changying Ling7
Estimated H-index: 7
(University of Wisconsin-Madison),
Kohei Nishimoto2
Estimated H-index: 2
(University of Wisconsin-Madison)
+ 3 AuthorsNathan V. Welham18
Estimated H-index: 18
(University of Wisconsin-Madison)
Fibrocytes (FCs) are hematopoietic lineage cells that migrate to sites of injury, transition to a mesenchymal phenotype, and help to mediate wound repair. Despite their relevance to human fibrotic disorders, there are few data characterizing basic FC biology. Herein, using proteomic, bioenergetic, and bioengineering techniques, we conducted deep phenotypic characterization of differentiating and mature FCs. Differentiation was associated with metabolic reprogramming that favored oxidative phosph...
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Published on Apr 1, 2019in Advanced Materials 21.95
Yan Wei12
Estimated H-index: 12
(Peking University),
Shengjie Jiang (Peking University)+ 11 AuthorsLili Chen (Huazhong University of Science and Technology)
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Published on Mar 1, 2019in Regenerative Medicine 2.99
Glyn Stacey6
Estimated H-index: 6
(University of Hertfordshire),
Peter W. Andrews60
Estimated H-index: 60
(University of Sheffield)
+ 17 AuthorsZoe Hewitt2
Estimated H-index: 2
(University of Sheffield)
Human stem cells have the potential to transform medicine. However, hurdles remain to ensure that manufacturing processes produce safe and effective products. A thorough understanding of the biological processes occurring during manufacture of what can be very complex products, is fundamental to assuring these qualities and thus, their acceptability to regulators and clinicians. Leaders in both human pluripotent and somatic stem cells, were brought together with experts in clinical translation, ...
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Published on Feb 1, 2019in Colloids and Surfaces B: Biointerfaces 4.00
Tingting Zhang1
Estimated H-index: 1
(Chinese Academy of Sciences),
Hong Chen1
Estimated H-index: 1
(Xi'an Jiaotong University)
+ 4 AuthorsRenjun Pei22
Estimated H-index: 22
(Chinese Academy of Sciences)
Abstract Many patients suffer from bone injury and self-regeneration is not effective. Developing new strategies for effective bone injury repair is highly desired. Herein, collagen, an important component of the extracellular matrix, was modified with glycidyl methacrylate. The water solubility and photochemical cross-linking ability of the resulting collagen derivative was then improved. Thereafter, BMSC-laden hydrogel was fabricated using collagen modified with glycidyl methacrylate and hyalu...
1 Citations Source Cite
Published on Jan 1, 2019in New Journal of Chemistry 3.20
Tingting Zhang1
Estimated H-index: 1
(Chinese Academy of Sciences),
Hong Chen (Chinese Academy of Sciences)+ 4 AuthorsRenjun Pei22
Estimated H-index: 22
(Chinese Academy of Sciences)
Collagen is the main protein and component of extracellular matrix, and it can promote the osteogenic differentiation of stem cells. Herein, a scaffold composed of carboxymethyl chitosan, hyaluronic acid and collagen was fabricated through covalent crosslinking, followed by investigating the physical and chemical properties of the scaffold. Thereafter, BMSCs were seeded into the scaffold and cultured in complete DMEM. The adhesion, proliferation and live/dead status of BMSCs in the scaffold were...
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Published on Dec 3, 2018in bioRxiv
Nicolas Valenzuela1
Estimated H-index: 1
,
Christopher Alt1
Estimated H-index: 1
+ 1 AuthorsEckhard Alt30
Estimated H-index: 30
(Tulane University)
Background: Freshly isolated, unmodified autologous adipose derived regenerative cells (ADRCs) (also named Stromal Vascular Fraction; SVF) have emerged as a promising tool for regenerative cell therapy. Due to regulatory concerns recently the use of cells recovered by non-enzymatic processing of adipose tissue has been suggested. The Transpose RT system (InGeneron, Inc., Houston, TX, USA) is a commercially available system for isolating ADRCs from adipose tissue. This system makes use of the pro...
1 Citations Source Cite
Published on Dec 1, 2018in Experimental Eye Research 3.15
Samantha Bobba4
Estimated H-index: 4
,
Nick Di Girolamo31
Estimated H-index: 31
(University of New South Wales)
+ 8 AuthorsAudra Shadforth6
Estimated H-index: 6
(Queensland University of Technology)
Herein, we review the safety, efficacy, regulatory standards and ethical implications of the use of stem cells in ocular disease. A literature review was conducted, registered clinical trials reviewed, and expert opinions sought. Guidelines and codes of conduct from international societies and professional bodies were also reviewed. Collated data is presented on current progress in the field of ocular regenerative medicine, future challenges, the clinical trial process and ethical considerations...
1 Citations Source Cite
Published on Dec 1, 2018in Stem Cell Research & Therapy 4.96
Giuliana Di Rocco11
Estimated H-index: 11
,
Silvia Baldari6
Estimated H-index: 6
+ 2 AuthorsGabriele Toietta18
Estimated H-index: 18
Background Cell therapy for degenerative diseases aims at rescuing tissue damage by delivery of precursor cells. Thus far, this strategy has been mostly unsuccessful due to massive loss of donor cells shortly after transplantation. Several strategies have been applied to increase transplanted cell survival but only with limited success. The endoplasmic reticulum (ER) is an organelle involved in protein folding, calcium homeostasis, and lipid biosynthesis. Protein disulfide isomerase (PDI) is a m...
1 Citations Source Cite