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The name doesn’t exactly hint at it, but Wharton’s jelly is at the forefront of current medical research. Its name dates back to the 17th century when the English anatomist Thomas Wharton first identified the jellylike substance that surrounds vital parts inside the umbilical cord. Today, it has become a distinct source of stem cells and, therefore, a critical element in advancing medical treatments for everything from hair loss, the treatment of wounds, and surgical procedures.
Found within Wharton’s jelly — which is easily harvested from what would otherwise be a post-natal medical waste — are several distinct stem cell genes. With this raw material, biomedical firms can create stem cell lines that, among other things, aid recuperation via the regeneration of tissue that has been lost or damaged.
This is because stem cells are, basically, the core building blocks of all human cells — which is why they are most prominently a part of human physiology during gestation in the womb. Stem cells, when retrieved from sources like Wharton’s jelly, are not dedicated to any specific bodily function. But their power is that they have the ability when introduced to other parts of the body, to adapt and grow — via division over an extended period of time (known as cell proliferation) — into other, more “mature” types of cells (known as potency):
Stem cells are unspecialized cells of the human body. They are able to differentiate into any cell of an organism and have the ability of self-renewal. Stem cells exist both in embryos and adult cells. There are several steps of specialization.
Current research is focused on growing a wide range of new tissue from stem cells, including muscle, blood, brain, and cartilage cells. It is an intricate field with remarkable potential.
There are currently four ways of sourcing stem cells. Each is now a distinct area of study and research, with the relative strengths and weaknesses of each methodology being probed and perfected:
This piece will focus on the medical technology being developed using Wharton’s jelly as a source material for stem cells, but will also delve into broader aspects of stem cell research, one of the most fascinating current areas of scientific study.
Stem cells are seen as one of the most important areas of current medical advancement. The potential uses for them are vast: from basic research leading to a better understanding of the source of birth defects and cancer to potential treatments for common conditions like arthritis, diabetes, and heart disease to treatments for rarer but severe conditions like spinal cord and brain injuries. It’s simply one of the most exciting fields not only in current medicine but in the sciences in general.
This is why, over the past few decades, so many resources have been dedicated to researching them. Since the initial discovery of the self-renewing properties of stem cells in the early 1960s — pioneered by a small team of researchers at the Ontario Cancer Institute — the understanding of the power and diversity of stem cells has increased rapidly. By the turn of the 21st century — as this an article published in 2004 in Current Opinion in Cell Biology states — their broad applicability was becoming clear:
Stem cells are defined by their capacity for self-renewal and multilineage differentiation, making them uniquely situated to treat a broad spectrum of human diseases. For example, because hematopoietic stem cells can reconstitute the entire blood system, bone marrow transplantation has long been used in the clinic to treat various diseases. Similarly, the transplantation of other tissue-specific stem cells, such as stem cells isolated from epithelial and neural tissues, can treat mouse disease models and human patients in which epithelial and neural cells are damaged. An alternative to tissue-specific stem cell therapy takes advantage of embryonic stem cells, which are capable of differentiating into any tissue type. Furthermore, nuclear transfer, the transfer of a post-mitotic somatic cell nucleus into an enucleated oocyte, creates a limitless source of autologous cells that, when combined with gene therapy, can serve as a powerful therapeutic tool.
There are now numerous peer-reviewed journals dedicated to the field, including as Stem Cell Research (established in 2007), Stem Cell Reports (established in 2013), and Stem Cells and Development (formerly the Journal of Hematotherapy, founded in 1992).
Today the full potential of stem cell therapies is still ascending. For a field of such intense study and development, there is still a sense of infinite possibilities, as was noted in the 2019 article entitled “Stem Cells: Past, Present, and Future”:
Stem cells have great potential to become one of the most important aspects of medicine. In addition to the fact that they play a large role in developing restorative medicine, their study reveals much information about the complex events that happen during human development…
Many serious medical conditions, such as birth defects or cancer, are caused by improper differentiation or cell division. Currently, several stem cell therapies are possible, among which are treatments for spinal cord injury, heart failure, retinal and macular degeneration, tendon ruptures, and diabetes type 1. Stem cell research can further help in better understanding stem cell physiology. This may result in finding new ways of treating currently incurable diseases.
The impact of this field of study is being felt already and will reshape human culture in the decades to come.
As has been mentioned, stem cells have not been without controversy. Especially in the United States — where the field has become intertwined in the politically potent anti-abortion movement — access to the most powerful type of stem cells (embryonic) creates challenges inside laboratories and medical facilities. Even though embryonic stem cells are extracted from embryos in laboratories (leftover from in vitro fertility treatments) and not from embryos in a woman’s womb, a significant minority of Americans objected to any experiments based on human embryos. This led to breaks in federal funding and restrictions in many states:
However, human stem cell (hSC) research also raises sharp ethical and political controversies. The derivation of pluripotent stem cell lines from oocytes and embryos is fraught with disputes about the onset of human personhood. The reprogramming of somatic cells to produce induced pluripotent stem cells avoids the ethical problems specific to embryonic stem cell research. In any hSC research, however, difficult dilemmas arise regarding sensitive downstream research, consent to donate materials for hSC research, early clinical trials of hSC therapies, and oversight of hSC research. These ethical and policy issues need to be discussed along with scientific challenges to ensure that stem cell research is carried out in an ethically appropriate manner. This article provides a critical analysis of these issues and how they are addressed in current policies.
This “third rail” has led to wild fluctuations in the policies under which researchers work while pursuing their studies and developing new medical treatments.
The crux of the issue circles back to the first two kinds of stem cells that were discovered, namely embryonic and adult:
Stem cells can be divided into two groups, embryonic and adult. Both types share the ability to self-renew and to differentiate into specialized cell types, but they differ in other attributes. Embryonic stem cells are derived during early development at the blastocyst stage and are pluripotent, meaning that they can differentiate into any cell type. Embryonic stem cells can be readily grown in culture and exhibit unique properties, including spontaneous differentiation into three germ layers in vitro or teratoma formation in vivo. In contrast, adult stem cells are rare, undifferentiated cells present in many adult tissues. Their primary role is to maintain and repair the tissue in which they reside. The ability of adult stem cells to differentiate is limited; these cells can be either multipotent or unipotent. Both embryonic and adult stem cells are studied as a promising source for clinical applications.
The fact is that embryonic stem cells are much better “tools” with which to work since they are far more versatile and can be dedicated to a wide range of medical uses.
Unfortunately, there is a very short window during which the body produces these kinds of cells. Once produced, they develop into a fetus that eventually grows to encompass all the 200-plus cell types that make up a human body.
Embryonic stem cells are grown from cells found in the embryo when it is just a few days old. In humans, mice and other mammals, the embryo is a ball of approximately 100 cells at this stage. It is known as a blastocyst and has two parts:
An outer layer of cells, or trophectoderm, will form the placenta that supports the embryo as it grows inside the uterus.
An inner clump of cells, called the inner cell mass, is a ball of 10–20 cells. These cells are undifferentiated, or unspecialized. They will multiply and differentiate extensively to make the many types of cells needed to form the entire animal. Some of the cells in the inner cell mass are pluripotent: they can make every type of cell in the body.
This reality creates a whole host of difficulties and challenges for medical researchers and clinicians seeking to harness the power of stem cells. The most powerful stem cells are produced by the human body over a very short time period and, thus, require access to a blastocyst.
But research eventually led to the discovery that other types of stem cells were still present during later stages of pregnancy:
The term perinatal encompasses the time from the 20th week of gestation to the neonatal period (the first 28 days of life). The tissue that sustains natal development is typically discarded as medical waste post-delivery. As such, harvesting stem cells from these tissues represent a safe, non-invasive means for attaining therapeutically beneficial stem cells. These include amnion/amniotic fluid, umbilical cord blood, placental tissue, umbilical cord vein, and the Wharton’s Jelly contained within the umbilical cord sometimes referred to as umbilical cord tissue.
Since directly accessing perinatal tissue in “real-time” is challenging for a host of technical, ethical, and political reasons, the next best time to access beneficial tissue is immediately after birth — from material that is otherwise discarded anyway.
Using perinatal stem cells — under which Wharton’s jelly falls — as a source of stem cell treatments, therefore, has two powerful foundations. One is that they offer a wide range of positive uses that will continue to multiply as research continues. The other is that they bypass the ethical and political issues that other sources of embryonic stem cells present.
The human umbilical cord is an increasingly popular source of cells being developed for cell therapy. The reasons, often reiterated, are the noninvasive harvest from tissue normally discarded at birth, the relatively high cell yields, and a phenotype that parallels that of mesenchymal stromal cells from other tissue sources. These cells are now being employed in human clinical trials, while also providing a cell source for an increasing number of preclinical and basic studies. Several recent reviews have highlighted the therapeutic efficacy of umbilical cord‐derived mesenchymal stromal cells and their potential advantages over other sources.
This in effect “clears the decks” of most ethical and political inhibitions on research and treatment development and has led to a concentration of attention about the uses that perinatal stem cells can be put.
In recent years this has led to a wide variety of programs in the United States that, according to the American Association of Tissue Banks (AATB), make the field one of the fastest-growing areas of tissue banking. The “total number of living tissue donors increased from fewer than 600 in 2007 to more than 19,000 in 2015,” according to their webpage, and from “2012 to 2015, the number of living tissue donors increased by 122% and now make up more than 13% of total tissue donors.”
This is not only an American phenomenon. The field is undergoing expansive growth globally. For example, Bentoluene International Health Concept, which works with mothers to encourage them to donate umbilical cords to blood banks, is a Nigerian medical services company whose director states: “The future of regenerative medicine holds much promise and cord blood is likely to play a major part in this advancement in our ability to treat human disease.”
A somewhat less imperative area of study is the use of Wharton’s jelly-products to treat hair loss:
Alopecia is caused by a variety of factors that affect the hair cycle and decrease stem cell activity and hair follicle regeneration capability. This process causes lower self-acceptance, which may result in depression and anxiety. However, early onset of androgenic alopecia is associated with an increased incidence of the metabolic syndrome and an increased risk of cardiac ischaemic disease. The ubiquity of alopecia provides an encouragement to seek new, more effective therapies aimed at hair follicle regeneration and neoregeneration. We know that stem cells can be used to regenerate hair in several therapeutic strategies: reversing the pathological mechanisms which contribute to hair loss, regeneration of complete hair follicles from their parts, and neogenesis of hair follicles from a stem cell culture with isolated cells or tissue engineering. Hair transplant has become a conventional treatment technique in androgenic alopecia (micrografts). Although an autologous transplant is regarded as the gold standard, its usability is limited, because of both a limited amount of material and a reduced viability of cells obtained in this way. The new therapeutic options are adipose-derived stem cells and stem cells from Wharton’s jelly. They seem an ideal cell population for use in regenerative medicine because of the absence of immunogenic properties and their ease of obtainment, multipotential character, ease of differentiating into various cell lines, and considerable potential for angiogenesis. In this article, we presented advantages and limitations of using these types of cells in alopecia treatment.
Though not a life-threatening condition, hair loss is an issue for over 55 million American (men and women) and effective treatment options are currently very limited.
Some of the most exciting, and important, possible uses of Wharton’s jelly therapies is in treating debilitating neurological disorders that destroy both the lives of those suffering from them and their families.
Alzheimer’s is a degenerative condition in which interneurons, which are the conduit for brain spinal cord cells to communicate with another, and brain cells themselves slowly die, which leads to profound memory loss and brain function. There is currently no cure and limited treatments, but Wharton’s jelly is now at the forefront of research into creating therapies that might reverse the ravages of Alzheimer’s.
A husband and wife team of Colombian scientists have observed Alzheimer’s precursor molecules in cells taken from newborns – a boon for research into the earliest stages of a disease that doesn’t start to show symptoms until people are in their forties.
This discovery, from the lab of Marlene Jimenez and Carlos Velez at the University of Antioquia in Medellin, Colombia, came about through a technique the pair developed to turn stem cells found in umbilical cord tissue into cholinergic neurons — a type of brain cell — in just days.
The cords were donated by mothers from families with a genetic mutation that causes early-onset Alzheimer’s disease, usually before age 50…
When the baby is born, the medical team cuts some 10 centimeters (4 inches) of the cord, which is then put into a tube, Velez said.
This sample is then sent to the Jimenez-Velez lab, where stem cells from a gelatinous tissue in the cord, called Wharton’s jelly, are then chemically coaxed into becoming neurons. The researchers can then watch how those cultured brain cells with and without the mutation differ.
Being able to create specific types of cells in the lab that would otherwise be difficult — or even unethical — to otherwise gain access to is a boon to researchers. It radically expands the depth and pace of medical research.
Parkinson’s disease, like Alzheimer’s, is a condition that can slowly ravage a person. It too is caused by the degradation of brain cells and neurons, in this case in the area of the brain controlling movement (this that causes a drop in the production of dopamine that results in a loss of control over parts of the body). Nerve endings are also destroyed, which leads to a host of other issues. But already there is a Wharton’s jelly-based treatment in development:
IMAC Holdings … today announced the United States Food and Drug Administration (the “FDA”) approved its investigational new drug application, which IMAC submitted in May 2020, for the use of umbilical cord-derived allogeneic mesenchymal stem cells for the treatment of bradykinesia, or the gradual loss and slowing down of spontaneous body movement, due to Parkinson’s disease.
The Company will now initiate enrollment of 15 patients for its Phase 1 trial to evaluate the safety and tolerability of the stem cell product acquired from technology developed by a major research university … utilizing intravenous administration of Wharton’s jelly-derived mesenchymal stem cells. The Company believes that the causes of bradykinesia may be related to an inflammatory response in the body. The Company’s new study is designed to confirm this belief and support the Company’s long-term strategy for the use of regenerative medicine in combination with physical rehabilitation to reduce the effect of movement-restricting diseases.
“Our regenerative rehabilitation centers have long focused on the importance of finding and applying non-opioid, non-surgical solutions to physical ailments in orthopedics. In 2017, our neurosurgeon researched opportunities to apply stem cells to treat Parkinson’s, and we put a team together to design a treatment for our neurological patients that simply could not achieve maximum benefit from physical therapy alone,” commented Jeffrey Ervin, IMAC’s Chief Executive Officer. “Having received approval to proceed with our study, IMAC is extremely optimistic regarding the potential of this stem cell technology. This has the potential to not only expand proprietary service options for neurological patients but also advance the way physically debilitating inflammatory conditions are managed as a whole.”
It cannot be overstated just how important breakthroughs in treating these kinds of neurological disorders would be. They are some of the most feared medical conditions that are a difficult fact-of-life for many older people — and their loved ones.
Another chronic — and ever more common — condition is diabetes, a cluster of diseases that wreak havoc with the body’s ability to regulate the level of glucose in the blood. This can lead to a whole cascade of problems, ranging from damaging blood vessels, eyes, kidneys, nerves, and significantly raising the risk of heart attack and stroke. Like with Alzheimer’s and Parkinson’s, the root issue is the degradation of key cells that have a specific function in the body.
But this too is an area in which Wharton’s jelly is seen as a way to advance the realm of what is possible.
Diabetes mellitus (DM) is an alarming metabolic disease in which insulin-secreting β-cells are damaged to various extent. Unfortunately, although currently available treatments help to manage the disease, however, patients usually develop complications, as well as decreased life quality and increased mortality. Thus, efficient therapeutic interventions to treat diabetes are urgently warranted. During the past years, mesenchymal stem cells (MSCs) have made their mark as a potential weapon in various regenerative medicine applications. The main fascination about MSCs lies in their potential to exert reparative effects on an amazingly wide spectrum of tissue injury. This is further reinforced by their ease of isolation and large ex vivo expansion capacity, as well as demonstrated multipotency and immunomodulatory activities. Among all the sources of MSCs, those isolated from umbilical cord-Wharton’s jelly (WJ-MSCs), have been proved to provide a great source of MSCs. WJ-MSCs do not impose any ethical concerns as those which exist regarding ESCs, and represent a readily available non-invasive source, and hence suggested to become the new gold standard for MSC-based therapies.
The fact that diabetes is one of the most prominent — and fastest-growing — adverse medical conditions in the world make the promise of Wharton’s jelly-based therapies a godsend. From 1980 to 2014 the number of people in the world with the condition rose from 108 million to 422 million. Any effective treatment will mark a medical turning point.
The breakdown and degradation of internal cell function is the root cause of many debilitating and tragic diseases. But the treatment of traumatic accidents and their long-term repercussions via emergency medicine or physical medicine and rehabilitation (PM&R) medicine are also areas where research and treatments are being enhanced with stem cell research.
One of the most exciting areas of such research and development is in the initial treatment of wounds. By developing wound dressings derived from Wharton’s jelly, researchers are finding ways to introduce cellular healing as early as possible in the medical process:
Corplex, a dehydrated human umbilical cord tissue, is offered in a sheet format as a wound covering or barrier membrane over acute and chronic wounds. The Corplex allograft is designed to retain both the epithelial layer and the hyaluronan-rich Wharton’s Jelly, heavily concentrated in extracellular matrix components such as glycosaminoglycans and collagen. The preservation of these structural components provides a robust matrix and protective barrier during wound remodeling.
These kinds of products could prove to be a leap forward for not only treating traumatic wounds but also for chronic wounds or non-healing ulcers (which is a common side effect of diabetes).
Likewise, the long-term repercussion of wounds is often scarring (which can also stem from surgery). Wharton’s jelly-based treatments are also being developed to lessen the severity of scars:
Wound healing requires an orchestrated integration of complex biological and molecular events, which include inflammation, proliferation, and remodeling. Despite the current use and availability of a wide array of wound dressings, ointments, and devices, wound healing still remains a clinical challenge, especially in older patients, diabetic patients, heavy smokers, or burned patients. Such wounds, if not treated effectively, eventually end up in amputations or disfiguring scars … Skin cell renewal is under the control of mesenchymal stem cells (MSCs). Skin MSCs populate the normal skin niche, remain quiescent, and become active after an injury, aiding in wound closure … Wharton’s jelly is an advantageous MSC source, because the harvest of this type of stem cells are not painful or invasive and because, in addition to their effect on wound healing, they seem to have a significant impact on the treatment of keloids.
This area of study has been intense over the past decade and continues to expand. It is currently one of the most advanced areas with regards to direct treatments based on stem cell technology.
Finally, Wharton’s jelly-based treatments are expected to be a boon to joint-related issues, whether chronic (arthritis and joint degeneration) or traumatic (injuries). The ability of clinicians to do more than simply remove or replace with prosthetics ligaments, tendons, and bones in joints — and instead instigate the regrowth of missing or damaged tissue — is an exciting new realm of medical science.
Such research and product development are well underway:
Ligament, muscle, and tendon injuries produce pain, loss of function, instability, and secondary osteoarthritis. Traditionally, these injuries have been managed using activity modification; physical therapy; pharmacological agents, such as non-steroidal anti-inflammatory drugs, corticosteroids, viscosupplementation, and narcotics; and surgical procedures when conservative management fails. These modalities have limitations and potential side effects … Over the last decade, there has been an increased interest in the use of biologics for regenerative medicine applications. Biologics currently used in clinical practice include platelet-rich plasma, bone marrow aspirate, adipose tissue aspirate, amniotic fluid, amniotic membrane, umbilical cord-derived Wharton’s jelly and cord blood. The healing capabilities of these products are attributed to the presence of stem cells, growth factors, cytokines, hyaluronic acid, and/or extracellular vesicles including exosomes.
By augmenting the wide range of treatments with techniques that can actually heal the root cause of pain and limited function — namely regenerating the missing or degraded tissue in the joint — the opportunity exists to radically improve joint mobility with minimally invasive procedures.
Very recently the Centers for Medicare & Medicaid Services (CMS) approved for payment two “Wharton’s jelly allografts” for the first time. The products — CoreText™ and ProText™ — are made by Regenative Labs and can be used to treat a number of medical conditions:
We work with dermatologists, diabetic specialists, orthopedists, surgeons, sports medicine physicians, and others to address the connective tissue supplementation needs of their patients,” said Tyler Barrett, CEO of Regenative Labs … According to CMS, both the products are intended to provide the extracellular matrix needed for the infiltration, attachment, and proliferation of cells required for the repair of damaged tissue. They are typically used for muscle and cartilage tears and to help repair damaged tissue. The products are used for wounds and tissue defects and are applied directly to the defect using a syringe.
This is an example of theoretical transitioning into the practical — a treatment that can be widely distributed and incorporated into daily medical practice.
A specific aspect of this last area of research — treating damaged knees — is now moving from ideal to practical. Currently severe, chronic knee issues stemming from osteoarthritis and rheumatoid and psoriatic arthritis often end with knee replacement (knee arthroplasty), which is the swapping out of problematic joint surfaces with artificial sections of metal or plastic that once again allows at least some pain-free motion of the knee.
This is an area that has been receiving the attention of the finest medical research facilities in the world, including Johns Hopkins Medicine:
Biomedical engineers at Hopkins have caused stem cells from adult goats to grow into tissue that resembles cartilage, a key step toward creating a minimally invasive procedure that may one day be used to repair injured knees, noses and other body parts.
In this method, doctors inject a fluid-filled with stem cells and nutrients into damaged tissue, then use light to harden the liquid into a stable gel. The researchers believe stem cells within the gel will multiply and form new bone or cartilage to replace the injured tissue.
Paving the way for this technique, the researchers have conducted lab experiments that turned stem cells within a gel into cartilage-like tissue.
These kinds of development bring into focus a future in which joint ailments are treated far less intrusively, without extended recovery times and the risk of infection from surgery.
Research has been moving forward in a wide variety of settings, including preliminary treatments for dogs suffering from knee osteoarthritis:
Significantly higher improvement in cartilage neogenesis and recovery was observed in the treated group compared to the untreated control group. The joint fluid and the inflammatory response in the treated group decreased. Moreover, improved recovery in the neogenetic cartilage, damaged skin fascia, and muscle tissue around the joints was more significant in the treated group than in the untreated control group.
In conclusion, canine UC-MSCs promote the repair of cartilage and patella injury in osteoarthritis, improve the healing of the surrounding tissues, and reduce the inflammatory response.
Successful clinical trials in other mammals pave the way for further treatments for humans, which are already underway:
A clinical trial involving patients with osteoarthritis (OA) taking place at the Krembil Research Institute is using stem cells to better understand and help find a cure for one of the most debilitating health problems of our day.
Supported by the Campaign to Cure Arthritis — which includes $3 million personally donated by all of the physicians and surgeons in the Arthritis Program at Toronto Western Hospital — the visionary study focuses on the evolving field of regenerative medicine to help reduce inflammation and replace lost cartilage.
The study at Krembil, the first North American mesenchymal stem cell trial for treating knee OA, could allow clinicians to repair damage biologically — at the source — rather than having to perform surgery to replace disease-ravaged joints in patients’ hips, knees, spines and shoulders.
The amount of momentum in the research community with regards to regenerative stem cell therapies is now intense.
And it is already leading to medical treatments now coming into use, including Wharton’s jelly-based products. These appear to be becoming some of the most promising new ways to treat the kind of damaged tissue that results in knee replacements:
Cell-based cartilage repair procedures are becoming more widely available and have shown promising potential to treat a wide range of cartilage lesion types and sizes, particularly in the knee joint. More recently, techniques have evolved from 2-step techniques that use autologous chondrocyte expansion to 1-step techniques that make use of mesenchymal stem cells (MSCs) embedded onto biocompatible scaffolding … Precursor MSCs can be isolated in abundance from the Wharton’s jelly of umbilical cord tissue. These cells have been shown to have the desired capacity for proliferation, differentiation, and release of trophic factors that make them an excellent candidate for use in the clinical setting to provide cell-based restoration of hyaline-like cartilage … The use of MSCs sourced from autologous tissue in combination with biocompatible scaffolding has shown encouraging clinical results at medium-term, comparable with more traditional methods of cell-based cartilage repair using autologous chondrocytes. The use of WJ-MSCe embedded scaffolds for cartilage repair procedures provides the additional potential advantages of off-the-shelf use and avoidance of morbidity related to autologous tissue harvest.
These kinds of treatments are now transitioning into reality, with a host of medical integrationists combining holistic treatments like chiropractic care, massage, physical therapy, and nutrition with cutting-edge, noninvasive healing technologies.
The ability to empower parts of the human body to regenerate cells is a powerful technological advance — and potentially life-altering to people who are suffering. Unlike geckoes that are able to grow back their tail, humans cannot regrow certain types of cells (brain cells or joint tissue) while other types often regrow with complications (skin).
Stem cell therapies give hope to a bright new day in medical technology that will empower human bodies to repair themselves in radically new ways, curtailing the use of artificial machinery in situations like knee replacements and — in the case of deeply feared and debilitative diseases like Alzheimer’s — giving people new hope.
With the ability to extract useful stem cell lines from perinatal materials that are routines disposed of as medical waste following births, a host of issues are minimized and potential medical development expanded. Wharton’s jelly has quickly become recognized as a powerful substance that is easy to access and in which a multitude of uses can be found.
 Wojciech Zakrzewski et al., “Stem Cells: Past, Present, and Future,” Stem Cell Research & Therapy 10, no. 68 (2019).
 “Stem Cells: What They Are and What They Do,” Mayo Clinic, n.d., https://www.mayoclinic.org/
 A. J. Becker, E. A. McCulloch, and J. E. Till, “Cytological Demonstration of the Clonal Nature of Spleen Colonies Derived from Transplanted Mouse Marrow Cells,” Nature 197 (1963): 452–54.
 Elizabeth A. Mayhall, Noëlle Paffett-Lugassy, and Leonard I. Zon, “The Clinical Potential of Stem Cells,” Current Opinion in Cell Biology 16, no. 6 (2004): 713–20.
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