Challenging Regeneration to Transform Medicine

Abstract

Summary The aging population in the U.S. and other developed countries has led to a large increase in the number of patients suffering from degenerative diseases. Transplantation surgery has been a successful therapeutic option for certain patients; however, the availability of suitable donor organs and tissues significantly limits the number of patients who can benefit from this approach. Regenerative medicine has witnessed numerous recent and spectacular advances, making the repair or replacement of dysfunctional organs and tissues an achievable goal. Public‐private partnerships and government policies and incentives would further catalyze the development of universally available donor tissues, resulting in broad medical and economic benefits. This article describes a Regenerative Medicine Grand Challenge that the Alliance for Regenerative Medicine recently shared with the White House's Office of Science and Technology Policy in response to a White House call to action in scientific disciplines suggesting that the development of “universal donor tissues” should be designated as a Regenerative Medicine Grand Challenge. Such a designation would raise national awareness of the potential of regenerative medicine to address the unmet needs of many diseases and would stimulate the scientific partnerships and investments in technology needed to expedite this goal. Here we outline key policy changes and technological challenges that must be addressed to achieve the promise of a major breakthrough in the treatment of degenerative disease. A nationalized effort and commitment to develop universal donor tissues could realize this goal within 10 years and along the way result in significant innovation in manufacturing technologies. Significance Regenerative therapies, in which dysfunctional or degenerating cells, tissues, or organs are repaired or replaced, have the potential to cure chronic degenerative diseases. Such treatments are limited by a shortage of donor organs and tissues and the need for immune suppression to prevent rejection. This article proposes a 21st Century Grand Challenge that would address this significant medical need by coordinating a national effort to convene the multidisciplinary expertise needed to manufacture functional and engraftable cells, tissues, or organs that could be made available to any patient without significant risk of rejection—so‐called universal donor tissues.

Human Mesenchymal stem cells program macrophage plasticity by altering their metabolic status via a PGE2-dependent mechanism

“…Several groups have indicated the presence of anti-inflammatory mediators such as PGE 2 in the induced MSC secretome313233. PGE 2 is generated from arachidonic derivatives through a COX2 -dependent Prostaglandin E synthase.…”

Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

“…In clinical trials, LCA patients also had improved visual ability, and multiple administrations to the same patient were declared safe; however, continue photoreceptor loss is not prevented in some patients (Ashtari et al, 2011; Bennett et al, 2016, 2012; Cideciyan et al., 2013). The backdrop of these seminal gene therapy trials and the pervading use of the CRISPR/Cas9 system (Bakondi et al, 2016; Suzuki et al, 2016; Wu et al, 2016) will allow gene therapy studies and personalized medicine to treat more patients with RP and other retinal degenerative diseases, yet with so many gene variants, targeting individual patients or genes may not be the most efficient route. Other more universal approaches may be needed to target patients with unknown gene mutations or larger patient populations in whole.…”

“…Each has specific tasks that they are able to perform within the retina, but may work synergistically when injected simultaneously or in tandem. Systemic delivery of MSCs may be able to offer immunomodulatory effects, which could allow for better engraftment of cells, such as RPE or NPCs (Bakondi et al, 2016; Maitra et al, 2004; Ren et al, 2008). Cells could also be pre-conditioned, as cells grown with different culture conditions have different gene expression profiles, or induced to overexpress growth factors for greater efficacy in vivo and RPE attachment to Bruch’s membrane (Afshari and Fawcett 2009; Gamm et al, 2007; Sugino et al 2014).…”

Presentation and treatments for Mucopolysaccharidosis Type II (MPS II; Hunter Syndrome)

“…Lentiviral vectors in ex vivo gene therapy have been used as a clinical option for several genetic diseases [140–143] and have been shown to be effective for correcting some aspects of neuronal defects in mouse models of MPS I and IIIA [144,140,145]. Lentiviral ex vivo HSC gene therapy improves biochemical abnormalities in tissues, rescues autophagic flux retardation, reduces neurofunctional impairments in the CNS, and decreases deterioration of the neuronal function of MPS II mice [140].…”