The pioneering induced pluripotent stem cell ipsc clinical study in japan led by top stem cell clinical researcher dr. The major objective was to assess safety, viability, and side effects. Pdf stemming retinal regeneration with pluripotent stem. Typical in vitrobased assays rely on treatment of clones by media containing growth factors that promote cell specification, for example, activin a, bmp4 and wnt3a, in the presence or absence of fbs without basic fgf. Retinal regeneration center for developmental biology riken cdb. The ogawayamanaka prize prize is meant to incentivize and honor those whose work is advancing the translational use of stem cells for regenerative medicine. To establish customized cell therapies originated from patients own cells, a group in japan led by masayo takahashi at the riken centre for developmental biology have relied on reprogramming cells from skin fibroblasts into induced pluripotent stem ips cells and then right into rpe. Jan 23, 2017 in this interview, masayo takahashi, project leader for laboratory for retinal regeneration, riken center for developmental biology kobe, japan explains the techniques being utilized in the first induced pluripotent stem cell ipsc clinical trial in humans. Developing rods transplanted into the degenerating retina.
He was involved in judo for more than 70 years, and was ranked hachidan eighthdegree black belt, making him one of the highest ranked canadian judoka. An ophthalmologist, takahashi was familiar with the ravages of amd, a condition that progressively damages the macula, the central part of the retina, and is the leading cause of blindness in the elderly. Masayo takahashi, who led the worlds first operation to implant induced pluripotent stem ips cells into a human body, says greater japanese understanding of the risks and benefits of new. Within 4 to 6 days, the cells are tested for gene and protein expression in embryonic lineages, including the classical markers pax6, brachyury and sox17 ectoderm, mesoderm and. Jun 19, 2016 retina specialist focuses on the latest advances in the diagnosis, medical management and surgical treatment of diseases of the retina, along with practical, realworld advice from leading clinicians and other experts on managing the successful retina practice. However, to our knowledge, b cell invasion and antibody in the inflamed retina after transplantation of retinal pigment epithelial rpe cells has not been reported. Last week, the woman, who is in her 70s, had a patch of the cells measuring 1.
Issuu is a digital publishing platform that makes it simple to publish magazines, catalogs, newspapers, books, and more online. His collaborator on this trial, masayo takahashi of the riken center for developmental biology in kobe, japan, had a head start. The newest development is that regulators in japan just have given conditional approval to an osaka university team to. The world economic forum is an independent international organization committed to improving the state of the world by engaging business, political, academic and other leaders of society to shape global, regional and industry agendas.
Retinal regeneration center for developmental biology. The trial was put on hold for several months due to regulatory changes in japan and concerns about mutations in an ips cell product to be used in the trial. Masayo takahashi world alliance forum in san francisco. Characterization of human induced pluripotent stem cellderived retinal pigment epithelium cell sheets aiming for clinical application author links open overlay panel hiroyuki kamao 1 2 michiko mandai 1 satoshi okamoto 1 noriko sakai 1 akiko suga 1 sunao sugita 1 junichi kiryu 2 masayo takahashi 1.
Harnessing the potential of stem cells to cure vision loss. David gamm, the pioneer of ips cellderived retinal differentiation and transplantation. Masayo takahashi is a pioneer in pushing the technology of ips cellderived cell types and actually introducing them into people. Nobelprizewinning stemcell researcher delivers keynote at. On the basis of the good results of preclinical studies, such as those on the use of subretinal ipscderived rpe in mice demonstrated by li et al.
Technological developments are required to overcome this, including automation instead of manual culture. View the profiles of people named masayo takahashi. After 5 days of coculture, the activity of the immune cells against the target rpe cells was evaluated by the proliferation of the immune cells. Clinicalgrade stem cellderived retinal pigment epithelium. Nobelprizewinning stemcell researcher delivers keynote. Preconditioning the initial state of feederfree human pluripotent stem cells promotes selfformation of threedimensional retinal tissue. The scientists at ucl have established a formal collaboration with pfizer for clinical development of a small patch of cells to cover the damaged macula, protecting the eye from agerelated blindness. Mar 19, 2018 an engineered patch of retinal pigment epithelium generated from human embryonic stem cells is transplanted into the eyes of two patients. Opsis is focused on discovering and developing novel medicines to treat retinal diseases and is a partnership with dr. Human embryonic and induced pluripotent stem cells hesc and hipsc have tremendous potential for clinical implementation. Japanese woman is first recipient of nextgeneration stem. Once the photo receptor cells have been lost, only the cell transplantation will cure. A threedimensional retinal tissue 3dretina is a promising graft source for retinal transplantation therapy. These cells were investigated by action potential analysis with manual and automatic planar patch clamp.
This spotlight article will describe the state of progress of some of the hpscderived. Agerelated macular regeneration amd is a refractory ocular disease that causes severe deterioration in central vision due to senescence in the retinal pigment epithelium rpe. Stem cell biotech biotime announced the news today that its subsidiary cell cure neurosciences cell cure has filed an ind with the fda for an embryonic stem es cellbased therapy for dry agerelated macular degeneration amd. Conventional thinking on diabetic retinopathy turned upside down. Sep 12, 2014 a japanese woman in her 70s is the first person to receive tissue derived from induced pluripotent stem cells, a technology that has created great expectations since it could offer the same. In these cases, blood vessels in the eye grow abnormally and lead to bleeding, the destruction of rpe cells, and eventual blindness. Evaluation of transplanted autologous induced pluripotent.
The eye represents an ideal microenvironment for stem cellbased therapy. The first trial in man using ips cells as a starting source for a cell therapy commenced in japan in 2014. Hoshimi kanemura, noriko sakai, masayo takahashi and masahiro j. Her mission is to cure diseases of blindness using ips cell technology. Stem cell transplantation to treat macular degeneration amdf. Modeling retinal degeneration using patientspecific.
Since the discovery of induced pluripotent stem cells ipsc in 2006, the symptoms of many human diseases have been reversed in animal models with ipsc therapy, setting the stage for future clinical development. Transplantation of ipscderived rpe sheet into first amd. We previously reported a technique for generating retinal pigment epithelia rpe and putative photoreceptors from embryonic stem es cells. Masayo takahashi which transplants rpe cells derived from ips cells into people with wet amd. Treating ipscs with wnt and nodal antagonists in suspension culture induced expression of markers of retinal.
Cell and gene therapy insights cell and gene therapies. However, a more ambitious goal is to develop cell therapeutics using hpscs to generate and replace somatic cells that are lost as a result of disease or injury. Detection of retinal pigment epitheliumspecific antibody in. Sep 15, 2014 the patient is part of the clinical study of autologous induced pluripotent stem cellderived retinal pigment epithelium rpe cell sheets for exudative amd, which is led by the riken cdbs masayo takahashi, m. She is the first of six people taking part in the landmark treatment developed by masayo takahashi and her colleagues at the riken center for developmental biology in kobe, japan. Treating macular degeneration amd with stem cells to. It is characterized by a progressive loss of photoreceptors in the macula due to damage to the retinal pigment epithelium rpe. The advancement of human pluripotent stem cellderived. Recently, ips cells from retinitis pigmentosa rp and gyrate atrophy patients were differentiated into rods and rpe and used to test the effects of drugs. Assessment of safety and functional efficacy of stem cell.
Fabricating retinal pigment epithelial cell sheets derived. Due to concerns about mutations and regulatory changes in japan, the trial was put on hold for several months. The developers also used a coated, synthetic membrane on which they assembled rpe cells differentiated from human escs and surgically delivered the patch. Here we show an optimized culture method for 3dretina generation from feederfree human pluripotent stem cells.
Kuwahara a, yamasaki s, mandai m, watari k, matsushita k, fujiwara m, hori y, hiramine y, nukaya d, iwata m, kishino a, takahashi m, sasai y, kimura t. Treating macular degeneration amd with stem cells to save. It is considered an immune privileged site, and the number of cells needed for therapy is relatively low for the area of focused vision macula. Easily share your publications and get them in front of issuus. Project leader masayo takahashi, md, explained that the woman had already failed at existing treatments.
Autologous induced pluripotent stem cell ipscderived retinal pigment epithelium rpe transplantation has been shown to improve visual function in animal models of agerelated macular degeneration amd and is currently being tested in human patients. To report the results after 4 years of followup in a previously presented first case of induced pluripotent stem cell ipscderived retinal pigment epithelium rpe sheet autologous. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. Phase 1 clinical study of an embryonic stem cellderived. Stem cells used in landmark therapy for failing sight. We report here that sdia induces efficient neural differentiation also in primate embryonic stem cells. Our research into retinal regeneration seeks to achieve clinical applications by developing methods for inducing stem cells or embryonic stem cells to differentiate into retinal neurons and pigment epithelial cells in sufficient. Jun 14, 2017 when she entered medicine in the mid1980s, masayo takahashi chose ophthalmology as her specialty, she said, because she wanted to have a family and thought the discipline would spare her from. Join facebook to connect with masayo takahashi and others you may know. The retinal pigment epithelium rpe is a single layer of cells that supports the lightsensitive photoreceptor cells that are essential for retinal. It is well known that the disease is caused by rod photoreceptor degeneration. Masayo takahashi is doing pioneering work using pluripotent stem cells as a basis for helping patients with vision loss such as due to macular degeneration.
The study uses autologous ips cells to derive rpes. Generation of dopaminergic neurons and pigmented epithelia. Masayo takahashi has been stopped reports the wsj in japan. An engineered patch of retinal pigment epithelium generated from human embryonic stem cells is transplanted into the eyes of two patients. Sep 17, 2014 stem cells used in landmark therapy for failing sight. The retina has been called the approachable part of the brain, owing to its relatively simple structure and its location near the body surface, and for these reasons it serves as a useful and experimentally amenable model of the central nervous system. In spite of all hurdles and controversy, clinical trials in treatment of spinal cord injury, macular degeneration of retina, type 1 diabetes and heart failure are already ongoing. To establish customized cell therapies originated from patients own cells, a group in japan led by masayo takahashi at the riken centre for developmental biology have relied on reprogramming cells from skin fibroblasts into induced pluripotent stem ips cells and then right into rpe cells. Project leader, laboratory for retinal regeneration in collaboration with the institute for biomedical research and. Masao takahashi june 24, 1929 february 14, 2020 was a canadian judoka, author, coach, and founder of the takahashi school of martial arts est. Characterization of human induced pluripotent stem cell.
Facebook gives people the power to share and makes the world more open and connected. Retinal pigment epithelial or rpe cells nourish the rods and cones. A strategy for personalized treatment of ipsretinal. It has since recommenced in june 2016 and many await the findings. Incorporated as a notforprofit foundation in 1971, and headquartered in geneva, switzerland, the forum is tied to no political, partisan or national interests.
Stem cells used in landmark therapy for failing sight new. Nov 14, 2017 antibodymediated rejection is characterized by donorspecific antibody produced by b cells. Rpe consists of a monolayer of cells situated between the photoreceptors and the choroid, and plays essential roles in photoreceptor. Finally, japanese researcher, dr masayo takahashi is leading a clinical trial in japan which transplants rpe cells made from ips cells into patients with wet amd.
Here we tested whether our procedure can promote retinal differentiation of mouse and human induced pluripotent stem cells ipscs. There is another clinical trial in japan led by japanese researcher dr. Treating macular degeneration amd with stem cells to save failing vision. Transplantation of autologous induced pluripotent stem cellderived retinal pigment epithelium cell sheets for exudative age related. We assessed the feasibility of transplanting a sheet of retinal pigment epithelial rpe cells differentiated from induced pluripotent stem cells ipscs in a patient with neovascular agerelated m.
Preconditioning the initial state of feederfree human. Apr 10, 2018 in these cases, blood vessels in the eye grow abnormally and lead to bleeding, the destruction of rpe cells, and eventual blindness. The authors showed that mice with retinal neuronal deficiency of aldh1a1 exhibited decreased vegf and sox9 production in rpe retinal pigment epithelium, and dorsal choroidal hypoplasia, which was phenocopied in mice with radeficient diet and also in mutant mice with rpe specific loss of sox9. Clinical studies using stem cells for treatment of retinal. Masao takahashi agenda contributor world economic forum.
Modeling retinal degeneration using patientspecific induced. Detection of retinal pigment epitheliumspecific antibody. Retinitis pigmentosa rp is the most common inherited human eye disease resulting in night blindness and visual defects. Dec 12, 2019 the retina is the main visual sensory tissue in mammals. Masayo takahashi, professor, riken center for biosystems dynamics research masayo takahashi received her m. A japanese lady in her 70s was the first patient to be treated by masayo takahashi and her team at the riken center for developmental biology kobe, japan. During retinal development, the optic cup derived from the rostral diencephalon is composed of inner and outer walls that differentiate into the neural retina nr and retinal pigment epithelium rpe, respectively.
She is a faculty member at the riken centre for developmental biology, a prominent female scientist in japan, and a bona fide stem cell champion. Prospects for clinical use of reprogrammed cells for. Shes the very first person in the world to successfully overcome all the regulatory barriers and the scientific barriers to introduce this new type of stem cell into a patient. It was a major thrill to have a nobelprizewinning scientist speak to our community, says stephen rose, ph. From the animal data it is clear that ipsc are rapidly becoming the lead cell type for cell replacement therapy and for the newly developing field of ipscderived body organ. However, oncogenic mutations might occur during the cell reprogramming process.
Agerelated macular degeneration amd bressler et al. Clegg discusses stem cell therapies for eye disease. The trial was put on hold for several months due to regulatory changes in japan and concerns about mutations in an ips cell product to be used in. We previously demonstrated that embryonic stem cells escs can generate 3dretina in vitro using a selforganizing stem cell culture technique known as sfebq. Jan 16, 2019 autologous induced pluripotent stem cell ipscderived retinal pigment epithelium rpe transplantation has been shown to improve visual function in animal models of agerelated macular degeneration amd and is currently being tested in human patients. Generation of retinal cells from mouse and human induced. Cell implants, genetic therapy, even optogenetics are.
She is the first of six people taking part in the landmark treatment developed by masayo takahashi and her colleagues at the riken center for. Masayo takahashi, takahashi masayo, born june 23, 1961 is a japanese medical physician, ophthalmologist and stem cell researcher takahashi serves as a project research leader at the riken center for developmental biology in kobe focusing on the clinical application of ips cell induced pluripotent stem cell technology on macular degeneration. Conventional thinking on diabetic retinopathy turned. Having followed closely the developments in programs using pluripotent based therapeutics i was fortunate during isscr2015 to have the opportunity to sit down with dr masayo takahashi to discuss her pioneering efforts to translate shinya yamanakas groundbreaking. Rpe sheet showed no sign of immune rejection during the one. Neural retinaspecific aldh1a1 controls dorsal choroidal. Human embryonic and induced pluripotent stem cells in. Feb 10, 2011 retinitis pigmentosa rp is the most common inherited human eye disease resulting in night blindness and visual defects. Photoreceptors or rods and cones enable us to see in day or night. Finally, in september 2015, cdi again strengthened its ips cell therapy capacity by setting up a new venture, opsis therapeutics. In 2014, japanese researchers led by masayo takahashi became the first to treat the wet form of amda severe type of amd that afflicts retinal blood vesselsby implanting scaffoldless sheets of rpe derived from induced pluripotent stem ips cells.
Autologous induced stemcellderived retinal cells for. Human pluripotent stem cells hpscs offer many potential applications for drug screening and disease in a dish assay capabilities. After an assistant professor in the department of ophthalmology, kyoto university hospital, she moved to the salk institute in 1995, where she discovered the potential of stem cells as a tool for retinal therapy. Gamm is working on a patch comprised of both photoreceptors and rpe to potentially restore vision to people with advanced retinal conditions. Jul 01, 2015 the pioneering induced pluripotent stem cell ipsc clinical study in japan led by top stem cell clinical researcher dr. Takahashi and her team were investigating the safety of ipscderived cell sheets in patients with wettype agerelated macular degeneration.
171 1164 1429 1401 217 376 1012 1019 1251 923 959 207 849 1068 1088 355 614 493 422 750 1334 1287 1433 239 192 242 330 213 105 822 458 537 120 1111 1462