Adult & Umbilical Cord Stem Cell Research (Ethical)

Umbilical Cord Stem Cells – Recent Research (Stem Cell Reviews)

"Stem Cells in the Umbilical Cord", by M. Weiss and E. Troyer, Stem Cell Reviews, Humana Press, vol.2, 2006
Abstract. "Stem cells are the next frontier in medicine. Stem cells are thought to have great therapeutic and biotechnological potential…Stem cells recovered postnatally from the umbilical cord, including the umbilical cord blood cells, amnion/placenta, umbilical cord vein, or umbilical cord matrix cells, are a readily available and inexpensive source of cells that are capable of forming many different cell types (i.e. they are 'multipotent')."
Introduction. Stem Cells Defined. Stem cells are defined simply as cells meeting 3 basic criteria:
First, stem cells renew themselves throughout life, i.e., the cells divide to produce identical daughter cells and thereby maintain the stem cell population.
Second, stem cells have the capacity to undergo differentiation to become specialized progeny cells. When stem cells differentiate, they may divide asymmetrically to yield an identical cell and a daughter cell that acquires properties of a particular cell type, for example, specific morphology, phenotype, and physiological properties that categorize it as a cell belonging to a particular tissue. Stem cells that may differentiate into tissues derived from all 3 germ layers (the ectoderm outer layer, the mesoderm middle layer, the endoderm inner layer) are called "pluripotent".
The [most popularized] example of pluripotent stem cells are the embryonic stem cells (ESCs) derived from the inner cell mass of early human embryos. In contrast with ESCs, most [non-embryonic] stem cells that have been well characterized are multipotent, i.e., they may differentiate into derivatives of 2 of the 3 germ layers.
The third property of stem cells is that they may renew the tissues that they populate. All tissue compartments contain cells that satisfy the definition of "stem cells", and the rate at which stem cells contribute to replacement cells varies throughout the body.

Abstract. "Stem cells are the next frontier in medicine. Stem cells are thought to have great therapeutic and biotechnological potential…Stem cells recovered postnatally from the umbilical cord, including the umbilical cord blood cells, amnion/placenta, umbilical cord vein, or umbilical cord matrix cells, are a readily available and inexpensive source of cells that are capable of forming many different cell types (i.e. they are 'multipotent')."
Introduction. Stem Cells Defined. Stem cells are defined simply as cells meeting 3 basic criteria:
First, stem cells renew themselves throughout life, i.e., the cells divide to produce identical daughter cells and thereby maintain the stem cell population.
Second, stem cells have the capacity to undergo differentiation to become specialized progeny cells. When stem cells differentiate, they may divide asymmetrically to yield an identical cell and a daughter cell that acquires properties of a particular cell type, for example, specific morphology, phenotype, and physiological properties that categorize it as a cell belonging to a particular tissue. Stem cells that may differentiate into tissues derived from all 3 germ layers (the ectoderm outer layer, the mesoderm middle layer, the endoderm inner layer) are called "pluripotent".
The [most popularized] example of pluripotent stem cells are the embryonic stem cells (ESCs) derived from the inner cell mass of early human embryos. In contrast with ESCs, most [non-embryonic] stem cells that have been well characterized are multipotent, i.e., they may differentiate into derivatives of 2 of the 3 germ layers.
The third property of stem cells is that they may renew the tissues that they populate. All tissue compartments contain cells that satisfy the definition of "stem cells", and the rate at which stem cells contribute to replacement cells varies throughout the body.

For example, blood-forming stem cells, gut epithelium stem cells, and skin-forming stem cells must be constantly replaced for normal health. In contrast, the stem cells in the nervous system that replace neurons are relatively quiescent and do not participate in tissue renewal or replace neurons lost to injury or disease.

In the body, stem cells live in specialized "niches", microenvironments including stem cell support cells, and extracellular matrix. The niche microenvironment regulates the growth and differentiation of stem cells. Understanding the role of the various "support" cells and the environment of the niche is helpful for in vitro manipulation and maintenance of stem cell populations. For example, a normal atmospheric oxygen concentration of 21% is relatively toxic to stem cells, and growth in "hyoxic" conditions of 2-3% oxygen is preferred…
When are Stem Cells Found? Stem cells have been isolated from virtually all of life's stages. That is, stem cells have been isolated from the inner cell mass of 5-day-old human embryos, as well as collected from the olfactory (nasal) epithelium of senior citizens…
Biomedical research conducted using postnatally collected (collected after birth) tissues and stem cells has generated [relatively no] controversy and has enjoyed more therapeutic applications to date. This is likely owing to the fact that blood and bone marrow stem cells were found to rescue patients with bone marrow deficiencies about 40 years ago. The result of this work produced the national bone marrow registry, which was established in the United States in 1986…
Sources of Stem Cells for Therapeutic Use. In the last 10 years, umbilical cord blood has been shown to be therapeutically useful for rescuing patients with bone marrow-related deficits and inborn errors of metabolism. Umbilical cord blood offers advantages over bone marrow because cord blood does not require perfect human leukocyte antigen (HLA) tissue matching, has less incidence of graft vs. host disease, and may be used allogenically. In addition, cord blood may be banked, and thus is available for use "off-the-shelf". Last y

ear, a federally supported program was established to expand the national umbilical cord blood banks to include a wide sample of HLA types. By 2004, there were more than 6000 cord blood stem cell units banked. As of January 2006, it is estimated that there are about 300,000 units in public and private banks in the United States.

Next to hematopoeitic (blood-producing) stem cells, the most widely studied stem cells in bone marrow are marrow-derived MSCs (Marrow Stromal Cells). MSC-like cells can be isolated from umbilical cord blood, placenta, amniotic fluid, and from the tissue surrounding the umbilical cord vessels, i.e., Wharton's Jelly. The collection of MSC-like cells from tissues that are discarded at birth is easier and less expensive than collecting MSCs from a bone marrow aspirate. During the collection of these tissues at birth, there is no health impact on either the mother or the newborn. At least in theory, these cells may be stored frozen and then thawed to provide stem cells for therapeutic use decades after cryogenic storage.
…The methods for isolating MSC-like cells are robust, i.e., labs throughout the world independently isolate MSC-like cells from umbilical cord tissues. This opens the door for independent verification, scalable production, and a large-team approach…
In umbilical cord blood, Kogler et al identified a cell that they call the universal somatic stem cell (USSC). The USSC is another rare cell (average of 16 cells in initial isolate; able to isolate USSC in 50% of the cords attempted). The USSC, like the MAPC (multipotent adult progenitor cell), offers much promise as an embryo-safe pluriporent cell. Widespread acceptance of these two cells will come when the methods for their isolation become robust such that any laboratory can isolate them and contribute to the field…
Properties of Umbilical Cord Matrix Stem Cells. Several groups have isolated MSC-like cells from the umbilical cord tissues or blood and have reported that those cells may express neural markers when differentiated, and differentiate into into neural (nerve) cells upon transplantation into rat brain. This is not too surprising, because adult bone marrow-derived MSCs injected into fetal rat brain engrafted, differentiated along neural-like lineages, and survived into the postnatal period (after birth)…
In 2003, we reported that UCM (umbilical cord matrix) cells can be induced in vitro to become cells with morphological and biochemical characteristics of neurons. These findings have been extended by others, for example, neurons, cardiac muscle, bone, and cartilage…
MSC-like cells derived from Wharton's Jelly adjacent to umbilical vessels (termed human umbilical cord perivascular cells) are also being studied…
Fu et al has reported that human UCM cells transplanted into hemi-parkinsonian rats prevented the progressive degeneration/deterioration in their Parkinson's disease model.
From these findings, it is suggested that UCM cells offer advantages over adult stem cells as a source of therapeutic cells.
First, UCM cells are derived from a noncontroversial, inexhaustible source, and can be harvested noninvasively at low cost.
Second, unlike human ESCs, UCM cells did not induce teratomas (tumors) or death after 1 x 106 to 6 x 106 human UCM cells were transplanted either intravenously or subcutaneously into severe combined immunodeficient beige mice (Rachakatla et al, unpublished).
Third, UCM cells are easy to start and do not require feeder layers or medium containing high serum concentrations to be maintained.
Fourth, they are not acutely rejected when transplanted as xenografts in nonimmune-suppressed rats. For example, we demonstrated that pig UCM cells undergo a moderated expansion following transplantation into rat brain without obvious untoward behavioral effects or host immune response…
Immune Suppression…[Many] data would support the hypothesis that UCM cells, like MSCs, may have immunosuppressive effects. We speculate that these effects may facilitate the engraftment of other therapeutic cells…
Homing. In addition to their immune-suppressive properties, MSCs appear to exhibit a tropism for damaged or rapidly growing tissues…There is now compelling evidence that MSCs, guided by chemokines and other cues emanating from areas of pathology such as tumors, will "home" specifically to those areas.
MSCs Support Expansion of Other Stem Cells…This work suggests that MSCs from a variety of sources, including umbilical cord, may facilitate engraftment of hematopoietic (blood producing) stem cells. Theoretically, this may enable transplantation of cord blood units into larger patients and speed the engraftment in other patients.
UCM Cells for Tissue Engineering. A major potential application of stem cells in medicine is for "tissue engineering", in which the ultimate goal is to provide off-the-shelf tissues and organs. UCM cells demonstrate excellent cell growth properties on bioabsorbable polymer constructs.
UCM cells were used to seed blood vessel conduits (making new blood vessels from stem cells) fashioned from rapidly bioabsorbable polymers and grown in vitro in a pulse duplicator bioreactor.
Recently, living patches engineered from UCM cells and cord-derived endothelial precursor cells have been described for potential use in human pediatric cardiovascular tissue engineering.
Summary. MSCs and MSC-like cells are useful multipotent stem cells that are found in many tissues. While MSCs can be isolated from adults via peripheral blood, adipose tissue, or bone marrow aspiration, MSCs derived from the discarded umbilical cord offer a low-cost, pain-free collection method of MSCs that may be cryogenically stored (banked) along with the umbilical cord blood sample. From the umbilical cord, isolation of cells from the Wharton's jelly has the greatest potential for banking, presently, because the most cells can be isolated consistently. 
The challenge of the future is to define industrial-grade procedures for isolation and cryoprese

rvation of umbilical cord-derived MSCs and to generate FDA-approved standard operating procedures (SOPs) to enable translation of laboratory protocols into clinical trials…Thus, more and more umbilical cord stem cells can be diverted from the biohazardous waste bag and into the clinic, where their life-saving potential can be realized. 

["Stem Cells in the Umbilical Cord", by M. Weiss and E. Troyer, Stem Cell Reviews, Humana Press, vol.2, 2006, www.HumanaJournals.com]
Umbilical Cord Blood-derived stem cells have proven clinically useful for numerous disease states, as have mesenchymal stem cells (MSCs) derived from bone marrow and adipose (fat) tissue. The recent identification of MSCs in umbilical cord blood (UCB) recognizes UCB as an "untapped resource for…therapeutic strategies" to replace injured or diseased connective tissue.
["Cord-Blood Mesenchymal Stem Cells and Tissue Engineering", by C. Cetrulo Jr, MD, Stem Cell Reviews, Humana Press, vol.2, 2006; 
www.HumanaJournals.com]