Ushering in the Era of Regenerative Medicine
Stem cell research and experimentation have been driving progress in the area of regenerative medicine for decades. Despite major advances in stem cell knowledge, current medical approaches rely on single drug or single molecule treatments, occasionally supported by removal or alteration of biological tissues by a surgeon’s scalpel.
There is irony in the term “modern” medicine, as the central focus in modern medicine has largely been to contain damage and to limit symptoms: “Diabetic? No problem, we can regulate your insulin.” Under our current framework for medicine, regeneration has not played a central role in treatment. Rather than welcome in regenerative treatments, fears of novel cell-based treatments have been perpetuated and an emphasis on drug-based treatments has been continued.
In contrast, the next decade will be ushering in an era of “futuristic” medicine, centered on remedying underlying health conditions and resolving states of health. Under this new model, what we currently consider “modern” medicine will soon be considered “archaic” medicine.
Life extension will also become a recognized area of medicine, referencing medical techniques that will allow for the extension of the average lifespan by 30-40 years. As Peter Diamondas, head of a Life Extension Company called Human Longevity, Inc, says, their vision is to “Make 100 the new 60.” In large part, progress in the area of regenerative medicine will be driven by cell-based therapies, with emphasis on delivering stem cells to sites of damage.
Exponential Growth of Stem Cell Technologies
The incorporation of stem cell technologies into modern medicine has been surprisingly slow. However, this makes sense when you recognize that (as with all areas of technology) advances with stem cells are following an exponential, and not linear, path of progress. Past accomplishments are only a small indicator of future progress that will be achieved.
Regardless, to become educated about the potential for future growth in stem cell technologies, it is valuable to educate yourself about historical events that have accompanied the discovery and evolution of stem cells. Both companies developing stem cell products and investors entering the stem cell sector can achieve improved decision-making through understanding technological advances that have driven breakthrough discoveries with stem cells to date.
Timeline of Landmark Events
The timeline below presents major accomplishments in stem cell research and development from 1860 to present (approximately a 150 year historical analysis). Enjoy!
|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. Johgn 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. Rudolf Jaenisch of the Salk Institute and Dr. Beatrice Mintz of the Fox Chase Institute created the first transgenic mammals” by inserting a virus that does not normally infect race into mouse embryos and watching the virus’s genes integrate into the embryonic cells as they developed into adult mice. This landmark creation of genetically modified mice set the stage 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 in 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 trails 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 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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