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A Timeline of Landmark Events in the Stem Cell Industry

Timeline: Landmark Developments in Stem Cell Development

Research and experimentation have been driving progress within the stem cell industry for decades. Despite major advances in stem cell knowledge, current medical approaches still rely heavily on pharmaceuticals and a surgeon’s scalpel. There is irony in the term “modern” medicine, because its central focus has largely been to address symptoms and not underlying medical issues. “Diabetic? No problem, we can regulate your insulin.”

Under our current framework for medicine, regenerative medicine has not played a central role.

Ushering in a New Era for Stem Cell Medicine

The next wave of medicine will be an era of regenerative medicine (RM) focused on resolving underlying health conditions, utilizing therapeutic approaches that include stem cell therapies, CAR-T cell therapies, and CAR-NK cell therapies.

Under this model, what we consider modern medicine will soon be archaic. As approaches to stem cell medicine make their way through clinical trials and into the marketplace, life extension will also become a recognized area of medicine.

As stated by Peter Diamandis, head of Human Longevity states, their vision is to “Make 100 the new 60.” Similarly, Celularity, Inc., co-founded by Peter Diamandis and Dr. Robert Hariri, has a mission to develop products that “augment immunity and longevity.”

Similarly, anti-aging researcher Aubrey de Grey has been vocal about his belief that aging is a disease that occurs through seven basic mechanisms, all of which he believes can be averted.

Unfortunately, the incorporation of regenerative approaches into medical practice been surprisingly slow.  However, medical advances with stem cells will follow an exponential, and not linear, path of progress. Past accomplishments are only a small indicator of future progress, a statement that is true of all technology advances – including computers, telecom, and artificial intelligence (AI).

Exponential Growth of Stem Cell Therapies

To understand part progress and future potential for stem cell therapies, it is valuable to know historical events that have accompanied the discovery and evolution of stem cells. The timeline below presents major accomplishments in stem cell research and development from 1860 to present.

YEAR DESCRIPTION OF EVENT
1860-1920 “Stem cells” inferred from analysis of embryo development and microscopy of bone marrow. (Germany)
1948-1958 Stem cell mechanisms deduced for sperm development and intestinal epithelium replacement. (Canada)
1958 First bone marrow transplants performed in human patients. (USA)
1958 Dr. John Gurdon of Oxford University reported cloning a tadpole with genetic characteristics of the original frog. He used a “nuclear transfer” approach in which scientists use the nucleus of a mature skin cell to replace the nucleus of an embryonic cell. (United Kingdom)
1959 Experiments in mice prove the existence of resident blood stem cells in marrow. (England)
1961 Dr. James Till and Dr. Ernest McCulloch of the Ontario Cancer Institute proved that stem cells exist. Stem cells are important because they can develop into any kind of tissue in the body. (Canada)
1968 First allogeneic human marrow transplants achieved avoiding lethal rejection reactions. (USA)
1969 First application of cell separation technology to dissect marrow stem cell hierarchy. (Canada)
1974 Dr. Beatrice Mintz of the Fox Chase Institute and Dr. Rudolf Jaenisch of the Salk Institute  created the first transgenic mammals by inserting a virus that does not normally infect mice into mouse embryos. They observed the virus’s genes integrate into the embryonic cells. This creation of genetically modified mice prepared the scientific community for the use of viruses to create animal models of human diseases. (USA)
1978 Transplantable stem cells are discovered in human cord blood. (USA)
1981 Dr. Gail Martin of the University of California, San Francisco, isolated stem cells from mice embryos. (USA)
1981 Drs. Marlin Evans and Matthew Kaufman of the University of Cambridge reported growing mouse embryonic stem cells in a petri dish. (United Kingdom)
1982 Marrow stem cells measured by regenerative capacity in vivo are shown to be distinct from progenitors measured by colony methods. (Australia, USA)
1982-1986 First methodology developed for targeted genetic modification in embryonic stem cells. (UK, USA)
1984 Blood stem cells measured by colony formation in vivo are first extensively purified. (Holland)
1990 Mouse marrow regenerating stem cells are first completely separated from in vivo colony-forming cells. (USA)
1992 Neural stem cells identified in the adult human brain. (Canada)
1993 Pluripotency of embryonic stem cells is proven through the generation of entirely embryonic stem cell-derived mice. (Canada)
1994 First separation of cancer stem cells from the majority of cells in a cancer. (Canada)
1994 Patients with damaged corneas are successfully treated with corneal stem cells. (Taiwan)
1995 First derivation of primate embryonic stem cell lines. (USA)
1996 Dr. Ian Wilmut of the Roslin Institute used Dr. Gurdon’s nuclear transfer method (see Dec. 1962) to clone a mammal (Dolly, the sheep), replacing the nucleus of a fertilized embroyo with the nucleus from an adult mammary gland cell. (United Kingdom)
1998 Dr. James Thomson of the University of Wisconsin isolated human embryonic stem cells. (USA)
2000 Retinal stem cells identified in mice. (Canada)
2001 First collaborative stem cell research network – the Stem Cell Network – is formed. (Canada)
2001 Dermal stem cells identified in adult skin tissue. (Canada)
2002 First complete purification from mice of multipotent marrow stem cells capable as single injected cells of extended marrow regeneration in vivo. (Canada)
2002 The International Society for Stem Cell Research is formed. (Global)
2002 Creation of the International Stem Cell Forum (ISCF) to encourage international collaboration, and with the overall aim of promoting global good practices and accelerating progress in biomedical science. (Global)
2003 Cancer stem cells isolated in human brain tumours. (Canada)
2003 Rare human breast cancer stem cells identified. (USA)
2004 First derivation of dopaminergic cells from human embryonic stem cells, a hope for Parkinson’s disease treatment. (USA)
2004 International Consortium of Stem Cell Networks (ICSCN) is initiated, which aims to unify international efforts to make stem cell therapy a reality for a broad range of debilitating diseases. (Global)
2005 First evidence for human bone cancer stem cells. (USA)
2005 James Till and Ernest McCulloch win the Lasker Prize for experiments that first identified stem cells and set the stage for all current research on adult and embryonic stem cells. (Canada)
2006 Normal mammary stem cells demonstrated in adult mice. (Australia, Canada, US)
2006 Drs. Shinya Yamanaka and Kazutoshi Takahashi at Kyoto University generated “embryonic stem – likes cells” by introducing four genes (later known as the Yamanaka factors) into mouse fibroblasts (a type of connective-tissue cell, which in this case where skin cells). They named the cells “induced pluripotent stem cells” or iPS cells. (Japan)
2007 Mario Capecchi, Martin Evans and Oliver Smithies win the Nobel Prize for Physiology for Medicine for discoveries enabling germline gene modification in mice. (United Kingdom, Global)
2007 First physical identification and localization of mammalian intestinal stem cells. (Holland)
2007 First evidence for human colon cancer stem cells. (Canada)
2007 Dr. Yamanaka and Takahashi repeated the same feat with human cells, reprogramming human adult skin cells into iPS cells (see 2006) that are comparable to human embryonic stem cells. (Japan)
2007 Dr. Yamanaka described a modified protocol for the generation of human iPS cells from adult skin cells without the c-Myc retrovirus – a retrovirus capable of forming tumors. (Japan)
2007 Dr. James Thomson of the University of Wisconsin reported a method for converting human skin cells into cells that closely resemble embryonic stem cells. (USA)
2007 Dr. Rudolf Jeanie of the Whitehead Institute applied iPS technology to treat a human disease in a mouse model, showing that reprogrammed iPS cells obtained from healthy skin cells could improve the symptoms of sickle cell-like anemia in mice. (USA)
2008 Sam Weiss is awarded the Gairdner Prize for the discovery of neural stem cells. (Canada)
2008 Dr. Jaenisch showed that iPS cells reprogrammed into neurons could improve symptoms in an animal model of Parkinson’s disease. (USA)
2008 Drs. Yamanaka and Keisuke Okita used a modified iPS protocol developed in 2007 to generate virus-free iPS cells. (Japan)
2009 John Gurdon and Shinya Yamanaka win the Lasker Prize for discoveries in nuclear reprogramming. Yamanaka is also awarded the Gairdner Prize. (Global)
2009 iPS cells created with minimal residual genomic alteration. (Canada)
2010 Adult cells reprogrammed directly to neurons, cardiac muscle and blood cells. (Canada, USA)
2010 iPS cells created by transfection of mRNA. (USA)
2010 First clinical trial of human embryonic-derived stem cells for treatment of spinal cord injury. (USA)
2010 Dr. Marius Wernig of Stanford University converted mouse skin cells into functional neurons in a petri dish. (USA)
2010 Dr. Deepak Srivastava of the Gladstone Institutes directly reprogrammed mouse non-muscle cells into beating heart cells. (USA)
2010 Dr. Mick Bhatia of McMaster University converted human skin cells directly into human blood cells. (Canada)
2010 Dr. Sheng Ding of Scripps Research Institute used only one factor and a cocktail of pharmaceutical chemicals to reprogram skin cells into iPS cells. (USA)
2011 Isolation of multipotent human blood stem cells capable of forming all cells in the blood system. (Canada)
2011 Dr. Sheng Ding, now of Gladstone Institutes, reveled methods of directly reprogramming adult skin cells into neurons that can transmit brain signals. (USA)
2012 John Gurdon and Shinya Yamanaka win the Nobel Prize in Physiology or Medicine for the discovery that mature cells can be reprogrammed to become pluripotent. (United Kingdom, Japan)
2012 Dr. Srivastava showed that scar tissue that formed after a heart attack can be directly reprogrammed into beating heart cells in living animals, significantly improving heart function and strength. (USA)
2012 Dr. Steven Finkbeiner of the Gladstone Institutes, along with the International Huntington’s Disease (HD) consortium, reprogrammed skin cells from HD patients to iPS Cells, developing the first-ever human cell-culture model of HD. (USA)
2012 Japanese researchers announced plans for the first human clinical trials using iPS cells to treat age-related macular degeneration – a leading cause of blindness. (Japan)
2012 Dr. Yadong Huang of Gladstone Institute transformed skin cells – with a single genetic factor – into neural stem cells that developed on their own into an interconnected functional network of mature brain cells. (USA)
2012 Dr. Yamanaka, laboratory at the Gladstone Institutes discovered that environmental factors critically influence the growth of IPS cells, taking an important step towards understanding how these cells develop – and towards the ability to use stem cell based therapies to combat disease. (USA)
2013 Induced pluripontent stem cells (iPSCs) enter the first ever clinical trial in humans, led by Masayo Takahashi of the RIKEN Center in Japan. The trial investigates the safety of iPSC-derived cell sheets for use in patients with macular degeneration. (Japan)
2014 A historic patent challenge occurs between a group called “BioGatekeeper” and Drs. Yamanaka and Takahashi, who hold a U.S. patent claiming a method for creating iPSCs (U.S. Patent No. 8,058,065).  (Global)

 

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