How old is stem cell
Oligopotent : These can differentiate into a few different cell types. Adult lymphoid or myeloid stem cells can do this. Unipotent : These can only produce cells of one kind, which is their own type. However, they are still stem cells because they can renew themselves. Examples include adult muscle stem cells. Embryonic stem cells are considered pluripotent instead of totipotent because they cannot become part of the extra-embryonic membranes or the placenta.
First, with the right stimulation, many stem cells can take on the role of any type of cell, and they can regenerate damaged tissue, under the right conditions. This potential could save lives or repair wounds and tissue damage in people after an illness or injury.
Scientists see many possible uses for stem cells. Until now, a person who needed a new kidney, for example, had to wait for a donor and then undergo a transplant.
There is a shortage of donor organs but, by instructing stem cells to differentiate in a certain way, scientists could use them to grow a specific tissue type or organ.
They can then repair a severe burn or another injury by grafting this tissue onto the damaged skin, and new skin will grow back. In , a team of researchers from Massachusetts General Hospital reported in PNAS Early Edition that they had created blood vessels in laboratory mice, using human stem cells.
Within 2 weeks of implanting the stem cells, networks of blood-perfused vessels had formed. The quality of these new blood vessels was as good as the nearby natural ones. The authors hoped that this type of technique could eventually help to treat people with cardiovascular and vascular diseases. Scientists could use stem cells to replenish the damaged brain tissue.
This could bring back the specialized brain cells that stop the uncontrolled muscle movements. Researchers have already tried differentiating embryonic stem cells into these types of cells, so treatments are promising.
Scientists hope one day to be able to develop healthy heart cells in a laboratory that they can transplant into people with heart disease. Similarly, people with type I diabetes could receive pancreatic cells to replace the insulin-producing cells that their own immune systems have lost or destroyed. The only current therapy is a pancreatic transplant, and very few pancreases are available for transplant.
Doctors now routinely use adult hematopoietic stem cells to treat diseases, such as leukemia , sickle cell anemia , and other immunodeficiency problems. Hematopoietic stem cells occur in blood and bone marrow and can produce all blood cell types, including red blood cells that carry oxygen and white blood cells that fight disease.
People can donate stem cells to help a loved one, or possibly for their own use in the future. Bone marrow : These cells are taken under a general anesthetic, usually from the hip or pelvic bone.
Technicians then isolate the stem cells from the bone marrow for storage or donation. Peripheral stem cells : A person receives several injections that cause their bone marrow to release stem cells into the blood. Next, blood is removed from the body, a machine separates out the stem cells, and doctors return the blood to the body. Umbilical cord blood : Stem cells can be harvested from the umbilical cord after delivery, with no harm to the baby. Some people donate the cord blood, and others store it.
For example, scientists have found that switching a particular gene on or off can cause it to differentiate. Knowing this is helping them to investigate which genes and mutations cause which effects.
Armed with this knowledge, they may be able to discover what causes a wide range of illnesses and conditions, some of which do not yet have a cure. Abnormal cell division and differentiation are responsible for conditions that include cancer and congenital disabilities that stem from birth. While most of the damaged DNAs are repaired by normal DNA repair mechanism, some of the mutated DNAs appear to escape from the repair mechanism and accumulate over time.
Accordingly, there would be a significant accumulation of mutated or damaged DNAs in aging cells compared to young cells. The accumulation of damaged DNA may in part be responsible for the various cellular events of the aging process. DNA damage impaired stem-cell function in aging, which has been documented by the study that HSCs derived from aged mice harbored significant alterations in their DNA repair response[ 1 , 17 ].
In satellite cells, H2AX phosphorylation was also accumulated with increasing age[ 67 ]. Premature aging can be resulted from defects in the DNA repair and telomerase pathway components in humans and mice[ 68 ]. In aging diseases, there has been significant interest in the telomere shortening that is now being used as a hallmark of aging, to which even stem cells are not immune[ 1 , 17 ].
A telomere is a region of repetitive nucleotide sequences at each end of a chromosome. It protects genome from nucleolytic degradation, unnecessary recombination, repair, or fusion with neighboring chromosomes[ 69 ]. When telomeres become critically short, the cell becomes senescent, it ceases to divide and may undergo apoptosis.
In fact, many aging-associated diseases, like the increased cancer risk[ 73 , 74 ], coronary heart disease[ 75 - 77 ], heart failure[ 78 ], diabetes[ 79 ], and osteoporosis[ 80 ], are caused by accelerated telomere shortening. Despite considerable evidence that telomere shortening causes reduction in life span, the telomere shortening concept of aging is still somewhat controversial, since laboratory mice lacking telomerase RNA component TERC showed no obvious abnormal phenotypes even after five generations[ 81 , 82 ].
Mitochondria are ubiquitous intracellular organelles in mammals and are the main source of cellular adenosine triphosphate ATP that plays a central role in a variety of cellular processes. In fact, there have been many studies suggesting a direct relationship between mitochondrial dysfunction and human stem cell aging[ 84 - 87 ]. Accordingly, in several cell systems, mitochondrial dysfunction has been shown to lead to respiratory chain dysfunction, which may be the result of the accumulation of mutations in mitochondrial DNA mtDNA [ 88 ].
In addition, it has been confirmed that mitochondrial aging interact with other cellular pathways of aging, such as the IGF-1 signaling and the mTOR pathways, which presumed to play a major role in aging[ 90 , 91 ]. Epigenetics refer to changes in gene expression, which are heritable through modifications without affecting the DNA sequence.
It has also been defined more broadly as the dynamic regulation of gene expression by sequence-independent mechanisms, including but not limited to changes in DNA methylation and histone modifications[ 92 - 94 ]. Epigenetic marks in stem cells are transmitted heritably to their daughter cells, priming lineage-specific loci for modification in downstream progenies[ 95 ].
Stem cell fates are regulated by epigenetic modifications of DNA that establish the memory of active and silent gene states[ 96 , 97 ]. Aberrant epigenetic regulation affects the organismal aging[ 98 ], age-associated dysfunction of stem cells, and predisposition to hematological cancers development[ 99 ].
For instance, DNA methylation specific to regions of the genome that are important for lineage-specific gene expression increased in aging HSCs[ ] and the perturbations of their histone modifications H3K4me3 may impair its self-renewal genes[ ]. Since most of the chromatin changes are intrinsically reversible, epigenetic alterations are therefore considered good therapeutic targets for molecular effectors and thereby are potential therapies for certain distinct pathologies[ , ].
Therefore, there has been immense interest in understanding these genome-scale regulatory mechanisms that lead to impaired gene expression, and that contribute to the decline of stem cell and tissue function with age. They are a class of small noncoding RNAs composed of to bp nucleotides[ ] that functions in RNA silencing and post-transcriptional regulation of gene expression[ - ]. It plays an important role in regulating stem cell self-renewal and differentiation by repressing the translation of selected mRNAs in stem cells and differentiating daughter cells[ ].
MiR— cluster seems to promote embryonic stem cell differentiation, self-renewal, and maintenance of pluripotency[ , ]. Moreover, recent findings show the involvement of miRNAs in senescence manipulation. These findings have led to the suggested use of these miRNAs as clinical biomarkers of stem cell senescence and their potentiality[ ]. In recent years with increasing understanding of stem cell behavior in different niche of the body offers promise for the development of potential therapeutic approaches to treat aging-associated dysregulation of adult stem cells and aging-related diseases.
Some of the potential therapeutic approaches for the treatment of age-related stem cell dysfunction are discussed below. The concept of parabiosis is not new; however, in the past decade its role in reversing the effects of aging and enhancing rejuvenation has gathered substantial momentum.
Recent findings suggest that aging-related cellular dysfunctions can be repaired successfully by modulating the molecular architecture of the tissue environment rather than inducing cell intrinsic changes alone[ ]. Therefore, the effects of aging in an old individual can be modulated or reversed by the circulatory or systemic factors derived from the young blood through anatomical joining, parabiosis[ 40 ].
The fascinating results of parabiosis have been reported to rejenuvate brain[ ], muscles[ 67 ], and liver tissues in the aged animals[ ]. In skeletal muscle regeneration, serum derived from young mice activated the Notch signaling pathway and regulated the satellite cells proliferation of old mice in vitro [ ].
In aged mice, through the parabiosis approach, systemic factors from young mice successfully reversed inefficient CNS remyelination, a regenerative process of CNS that produces new myelin sheaths from adult stem cells[ ].
Despite the promising outcomes in animal models, there is persistence of contradiction in functions of factors identified in prominent parabiosis studies, rendering the concept highly controversial for use in humans. For instance, growth differentiation factor 11 GDF has been reported to show both positive[ 67 ] and negative corelations[ ] with stem cell aging.
Retrotansposons are mobile DNA elements that can induce genetic instability and have been reported to be a cause of cellular dysfunction during aging[ ].
The long interspaced nuclear elements L1 are 6-kb long retrotransposons that code for RNA binding protein and endonuclease protein. There are copies of L1 elements in the human genome, and approximately of such active elements replicated to induce genomic instabilities and to increase the risk of DNA damage.
Elevated activity of L1 has been reported in aging-related pathological conditions[ ]. The link between SIRT-6 an important marker of longevity and L1 offered more direct evidence for the role of L1 in aging-related genomic complications. SIRT6 are known to repress the activity of L1 retrotransposons[ ]. DNA damage-induced mobilization of SIRT6 to the site of repair and subsequent repression of L1 have been contemplated in the development of therapeutics for age-related neurological pathologies, such as dementia and cancer[ ].
Suppression of L1 activity by overexpression of SIRT6 in senescence cells delayed the onset of L1-induced pathological conditions. Other than modulation of SIRT6 expression, inhibition of reverse transcriptase a critical enzyme for the L1 replication is another way to attenuate L1 activity[ ]. Cellular reprogramming of aged somatic cells towards iPSC enables the editing and resetting of the cellular clock by removing the characteristic feature of aging.
The ability to derive iPSCs from aging-related pathological cells have enabled investigators to develop recombination-based therapeutic approaches to edit genetic defects responsible of premature and accelerated aging.
The reprogramming of aged somatic cells to target stem can be used as an alternative source to get cells for transplantation and for genetic editing. Recent studies show encouraging effects of reprogramming in rejuvenation of senescent cells, as evident by elongated telomeres and reduced oxidative stress[ ]. Valuable information from these studies has resulted in the first clinical trial for progeroid patients[ ].
In a mouse model of skeletal defect, human iPSC designed to express PAX7 were able to be differentiated into muscle progenitor cells that engrafted and repaired the defective dystrophin-positive myofibers formation.
As discussed above, the telomere length is inversely linked to the chronical age, and thus it is believed that increasing the length of telomere may increase life span. Many advanced approaches are being developed to efficiently increase the telomere length and to protect cells from chromosome shortening. In in vitro cultured human cells, the delivery of RNA coding for telomere-extending protein has been reported to increase the cell proliferation rate[ ].
In telomere-deficient mice, genetic editing to reactivate telomerase activity has been reported to reverse the aging symptoms[ ]. Telomerase activation drugs and telomerase gene therapy are also alternative approaches that aim to increase the telomere length to protect the cells from premature aging[ , ]. From the various advances in stem cell research, it is clear that we grow old partly because our stem cells grow old with us.
The functions of aged stem cells become impaired as the result of cell-intrinsic pathways and surrounding environmental changes. With the sharp rise in the aging-associated diseases, the need for effective regenerative medicine strategies for the aged is more important than ever.
Fortunately, rapid advances in stem cell and regenerative medicine technologies continue to provide us with a better understanding of the diseases that allows us to develop more effective therapies and diagnostic technologies to better treat aged patients.
However, there is a big ethical concern regarding the use of human embryos to procure embryonic stem cells and many countries already currently restrict experiments on embryos to the first 14 d. Additionally, the International Society for Stem Cell Research has issued guidelines advising researchers across the globe to stick with this d window.
Conflict-of-interest statement: The authors have declared that no conflict of interest exists. Manuscript source: Invited manuscript. Specialty type: Medicine, research and experimental.
Country of origin: United States. Peer-review report classification. Grade A Excellent : 0. Peer-review started: August 29, First decision: November 14, Article in press: December 9, National Center for Biotechnology Information , U. World J Exp Med. Published online Feb Author information Article notes Copyright and License information Disclaimer. Published by Baishideng Publishing Group Inc. All rights reserved. This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers.
This article has been cited by other articles in PMC. Abstract Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells.
Open in a separate window. Figure 1. Microenvironment Aging is characterized by common environmental conditions, such as hormonal, immunologic, and metabolic disorders[ 48 - 50 ] and these are considered as the critical microenvironmental factors affecting stem cell functions. DNA damage and telomere shortening In mammals, spontaneous and extrinsic mutational events occur on DNA on daily basis.
Mitochondrial dysfunction Mitochondria are ubiquitous intracellular organelles in mammals and are the main source of cellular adenosine triphosphate ATP that plays a central role in a variety of cellular processes. Epigenetic alteration Epigenetics refer to changes in gene expression, which are heritable through modifications without affecting the DNA sequence. Parabiosis The concept of parabiosis is not new; however, in the past decade its role in reversing the effects of aging and enhancing rejuvenation has gathered substantial momentum.
Retrotansposons Retrotansposons are mobile DNA elements that can induce genetic instability and have been reported to be a cause of cellular dysfunction during aging[ ]. Cellular reprogramming towards iPSCs iPSCs are a type of pluripotent stem cell that can be generated directly from adult cells and the recent advances in this area have opened up many gateways for the research in cell-based therapeutics[ ].
Telomere lengthening As discussed above, the telomere length is inversely linked to the chronical age, and thus it is believed that increasing the length of telomere may increase life span.
Footnotes Conflict-of-interest statement: The authors have declared that no conflict of interest exists. References 1. How stem cells age and why this makes us grow old.
Nat Rev Mol Cell Biol. The good and the bad of being connected: the integrons of aging. Therapeutic cloning, also called somatic cell nuclear transfer, is a technique to create versatile stem cells independent of fertilized eggs.
In this technique, the nucleus, which contains the genetic material, is removed from an unfertilized egg. The nucleus is also removed from the cell of a donor. This donor nucleus is then injected into the egg, replacing the nucleus that was removed, in a process called nuclear transfer. The egg is allowed to divide and soon forms a blastocyst. This process creates a line of stem cells that is genetically identical to the donor's cells — in essence, a clone.
Some researchers believe that stem cells derived from therapeutic cloning may offer benefits over those from fertilized eggs because cloned cells are less likely to be rejected once transplanted back into the donor and may allow researchers to see exactly how a disease develops. Researchers haven't been able to successfully perform therapeutic cloning with humans despite success in a number of other species.
However, in recent studies, researchers have created human pluripotent stem cells by modifying the therapeutic cloning process. Researchers continue to study the potential of therapeutic cloning in people. There is a problem with information submitted for this request.
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This content does not have an Arabic version. See more conditions. Stem cells: What they are and what they do. Products and services. Stem cells: What they are and what they do Stem cells and derived products offer great promise for new medical treatments.
By Mayo Clinic Staff. Open pop-up dialog box Stem cells: The body's master cells Close. Stem cells: The body's master cells Stem cells are the body's master cells. Thank you for Subscribing Our Housecall e-newsletter will keep you up-to-date on the latest health information. Please try again. Something went wrong on our side, please try again. National Institutes of Health. Accessed July 23, Stem cell basics. In many tissues, adult stem cells are at the root of this process, tasked with supplying cells to maintain normal tissue function and facilitating regeneration in response to injury.
It is logical then to assume that, as our bodies grow older and our organs and faculties begin to degenerate, our stem cells must be failing us. In fact, much research has gone into uncovering what happens to our stem cells as they age. For example, hematopoietic stem cells, which produce all the cells of the blood and immune system, actually increase in number in aging adults.
Unfortunately, the expansion in cell numbers is to compensate for their overall loss in functionality. Ultimately, fewer white blood cells are produced, which contributes to a deficient immune system and diminished resistance to disease and infections in the elderly.
One fascinating avenue of research focuses on what happens to stem cells in the brain as we age.
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