Stem Cell History.. and the STEM CELL FACTS !

There are three basic types of stem cells. Totipotent stem cells, meaning their potential is total, have the capacity to give rise to every cell type of the body and to form an entire organism.

Pluripotent stem cells, such as embryonic stem cells, are capable of generating virtually all cell types of the body but are unable to form a functioning organism.

Multipotent stem cells can give rise only to a limited number of cell types. For example, adult stem cells, also called organ- or tissue-specific stem cells, are multipotent stem cells found in specialized organs and tissues after birth. The stem cell fact is is most important to remember is that their primary function is to replenish cells lost from normal turnover or disease in the specific organs and tissues in which they are found.

Totipotent stem cells occur at the earliest stage of embryonic development. The union of sperm and egg creates a single totipotent cell. This cell divides into identical cells in the first hours after fertilization. Stem Cell Facts make many people think about their own MORTALITY. FACT: All these cells have the potential to develop into a fetus when they are placed into the uterus.

The first differentiation of totipotent cells forms a hollow sphere of cells called the blastocyst, which has an outer layer of cells and an inner cell mass inside the sphere.

Another interesting stem cell fact,is that the outer layer of cells will form the placenta and other supporting tissues during fetal development, whereas cells of the inner cell mass go on to form all three primary germ layers: ectoderm, mesoderm, and endoderm.
The three germ layers are the embryonic source of all types of cells and tissues of the body. Embryonic stem cells are derived from the inner cell mass of the blastocyst. They retain the capacity to give rise to cells of all three germ layers.

However, embryonic stem cells cannot form a complete organism because they are unable to generate the entire spectrum of cells and structures required for fetal development. Thus, embryonic stem cells are pluripotent, not totipotent, stem cells.

Stem Cell Facts continued

... Embryonic germ (EG) cells differ from embryonic stem cells in the tissue sources from which they are derived, but appear to be similar to embryonic stem cells in their pluripotency. Human embryonic germ cell lines are established from the cultures of the primordial germ cells obtained from the gonadal ridge of late-stage embryos, a specific part that normally develops into the testes or the ovaries.

Embryonic germ cells in culture, like cultured embryonic stem cells, form embryoid bodies, which are dense, multilayered cell aggregates consisting of partially differentiated cells.

An interesting stem cell fact is that the embryoid body-derived cells have high growth potential. The cell lines generated from cultures of the embryoid body cells can give rise to cells of all three embryonic germ layers, indicating that embryonic germ cells may represent another source of pluripotent stem cells.

Much of the knowledge about embryonic development and stem cells has been accumulated from basic research on mouse embryonic stem cells.

Since 1998 .. here's another stem cell fact worth remembering:

Research teams have succeeded in growing human embryonic stem cells in culture. Human embryonic stem cell lines have been established from the inner cell mass of human blastocysts that were produced through in vitro fertilization procedures.

The techniques for growing human embryonic stem cells are similar to those used for growth of mouse embryonic stem cells. However, human embryonic stem cells must be grown on a mouse embryonic fibroblast feeder layer or in media conditioned by mouse embryonic fibroblasts.

Human embryonic stem cell lines can be maintained in culture to generate indefinite numbers of identical stem cells for research. As with mouse embryonic stem cells, culture conditions have been designed to direct differentiation into specific cell types (for example, neural and hematopoietic cells).

Adult stem cells occur in mature tissues. Like all stem cells, adult stem cells can self-replicate. Their ability to self-renew can last throughout the lifetime of individual organisms is a stem cell fact relating to own adult stem cells comprise the body's Renewal System.

But unlike embryonic stem cells, it is usually difficult to expand adult stem cells in culture. Adult stem cells reside in specific organs and tissues, but account for a very small number of the cells in tissues.

This Stem cell fact is Proven over & over ...Adult stem cells are responsible for maintaining a stable state of the specialized tissues. To replace lost cells, stem cells typically generate intermediate cells called precursor or progenitor cells, which are no longer capable of self-renewal. However, they continue undergoing cell divisions, coupled with maturation, to yield fully specialized cells.

It must be noted that included in these Stem cell facts... are that stem cells have been identified in many types of adult tissues, including bone marrow, blood, skin, gastrointestinal tract, dental pulp, retina of the eye, skeletal muscle, liver, pancreas, and brain.

An interesting stem cell fact is that adult stem cells are usually designated according to their source and their potential. Adult stem cells are multipotent because their potential is normally limited according to their source and their potential.

However, a special multipotent stem cell that can be found in bone marrow, called the mesenchymal stem cell, can produce all cell types of bone, cartilage, fat, blood, and connective tissues.

Blood stem cells, or hematopoietic stem cells, are the most studied type of adult stem cells. The concept of hematopoietic stem cells is not new, since it has been long realized that mature blood cells are constantly lost and destroyed. Billions of new blood cells are produced each day to make up the loss. This process of blood cell generation called hematopoiesis, occurs largely in the bone marrow.

Another emerging source of blood stem cells is human umbilical cord blood. Similar to bone marrow, umbilical cord blood can be used as a source material of stem cells for transplant therapy. However, because of the limited number of stem cells in umbilical cord blood, most of the procedures are performed for young children of relatively low body weight.

Neural stem cells, the multipotent stem cells that generate nerve cells, are a new focus in stem cell research.

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Active cellular turnover does not occur in the adult nervous system as it does in renewing tissues such as blood or skin. Because of this observation, it had been a dogma that the adult brain and spinal cord were unable to regenerate new nerve cells.

However, since the early 1990s, neural stem cells have been isolated from the adult brain as well as fetal brain tissues. Stem cells in the adult brain are found in the areas called the subventricular zone and the ventricle zone.

Another location of brain stem cells occurs in the hippocampus, a special structure of the cerebral cortex related to memory function. Stem cells isolated from these areas are able to divide and to give rise to nerve cells (neurons) and neuron-supporting cell types in culture.

See also Cell differentiation; Embryology; Embryonic differentiation; Germ layers; Hematopoiesis; Regeneration (biology); Transplantation biology.

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CLICK HERE ..The Healing Power of your Own Adult Stem Cells explained by a Doctor

Stem Cell Facts.. Demystified

Indeed, as discoveries seems to outmaneuver controversy, Stem Cells and their enormous potential for use in clinical therapy, are the focus of much interest and debate. However, stem cell facts and history,including the medical jargon and the dissemination of scientific information to the general public can be quite confusing and rather overwhelming for the uninitiated.

If you have had the need to seek out more stem cell facts or stem cell therapy options, then the chances are that you may already have familiarized yourself with certain terminologies in the field. What follows is a synopsis of pertinent stem cell facts, concepts, procedures and terminologies that should simplify matters, inform you further, and empower your effective decision-making.

What is a Stem Cell?

Stem cells are undifferentiated cells. Pluri– or totipotent stem cells have the potential, given the required microenvironment, to develop from a progenitor or parent cell into each cell type of the human body. When stem cells are referred to as being multipotent then their developmental capacity is a bit more limited and they have an ability to differentiate into many, but not all, cell types (thus multi lineages). Stem cells are capable of dividing and renewing themselves infinitely, acting as a regeneration and maintenance system.

The potency of stem cells makes them key to developing new regenerative and transplant cures.

Embryonic Versus Adult Stem Cells

The term adult stem cell is used for any stem cell derived from the postnatal animal (especially the human) to differentiate it from embryonic stem cells. Use of, and research on human embryonic stem cells is controversial, with debate focusing on moral and ethical concerns. Adult stem cells are typically sourced from bone marrow, fat, umbilical cord and placenta.

Source of Cells

1. Embryo Embryonic stem cells are a population of self-renewing, pluripotent cells that are derived from the inner cell mass of mammalian embryos at the blastocyst stage (3 - 4 days after conception). These cells are the most versatile of the stem cell group, having the ability to transform or differentiate into any cell in the human body. Differentiation is dependent on micro-environmental cues. Development, broadly speaking, follows a haematopoeitic (blood) or a non-haematopoeitic lineage.

The moral and ethical issues surrounding the use of human embryonic stem cells have frustrated efforts for medical advancement. Scientists have proposed a new and less controversial source of embryonic stem cells; human eggs discarded in fertility treatments - up to 1/3 of eggs used during in vitro fertilisation are found to be unusable and consequently discarded.

2. Umbilical Cord and Placenta Stromal cells isolated from the human umbilical cord mesenchymal tissue, namely Wharton's jelly, have been shown to exhibit stem cell potency. Since umbilical cord is a postnatal organ discarded after birth, the collection of cells does not require an invasive procedure with ethical concerns. Placentas also, are typically thrown away by hospitals and are a source of mesenchymal stems cells.

Mesenchymal stromal cells of foetus-derived tissue possess multipotent properties between embryonic stem cells and adult stem cells. They can be successfully differentiated into mature adipocytes, osteoblasts, chondrocytes, skeletal myocytes, cardiomyocytes, neurons and endothelial cells. More on mesenchymal cells later!

3. Bone marrow Bone marrow, particularly of the long bones, is the source of haematopoetic stem cells that have been used for the past several years in transplants. There are no ethical issues regarding their use, but the method for accessing them is invasive.

Cell Types

1. Mesenchymal stromal cells (MSC) Mesenchymal cells are considered to be multipotent adult progenitor cells that possess stem cell features. They have a considerable capacity for self-renewal while maintaining their multipotency.

These stem cells can differentiate into a range of different cell types (related tissue types are in brackets) associated with the musculoskeletal system such as osteoblasts (bone), chondrocytes (cartilage), adipocytes (fat), myocytes (muscle), myofibroblasts (tendon and ligament). Their ability to give rise to cells of non-musculoskeletal tissue such as brain or liver or pancreatic islets cells has been reported.

Given this potential, mesenchymal stem cells make excellent candidates for use in treating a range of tissues affected by disease or damage; tissue remodeling depends on mesenchymal cells. As previously mentioned, these cells can be derived from Wharton's jelly present in the umbilical cord.

Allogeneic transplantation of mesenchymal stem cells between different individuals may also be possible as these cells appear to be immune privileged in that they are not necessarily rejected when implanted into unmatched recipients.

2. CD34 + cells These are haematopoietic stem cells, found in umbilical cord and bone marrow, with cell surface markers specific for CD34. The CD 34 molecule functions in cell-to-cell adhesion (CD is an abbreviation for: cluster of differentiation). CD34+ cells may be useful in several areas of clinical stem cell transplantation, including stem cell expansion and haematopoietic recovery. As a matter of clinical distinction, mesenchymal cells are CD34 negative.

What is Stem Cell Therapy?

This novel kind of therapy has as its basic tenet that stem cells recruited to sites of injury are involved in tissue repair, regeneration, and remodelling. Stem cells are isolated from cord blood or other, cultured in a laboratory and then therapeutically applied to ameliorate degenerative diseases, and serious injury in patients.

The hope is that human stem cells can be used to heal patients with Alzheimer's, Parkinson's disease, diabetes, liver disease, multiple sclerosis and other chronic diseases.

What Does Cell Culture Entail? An essential prerequisite to the successful development of stem cell-based therapies is the development of techniques to propagate pure populations of stem cells on a large scale.

Mesenchymal stem cells are very rare, existing at an estimated frequency of about 1 in 100,000 bone marrow cells(1). To obtain sufficient numbers, cells are encouraged to multiply indefinitely in the laboratory. Briefly, the process entails isolating cells from a source such as umbilical cord and growing them up in a cell culture facility whereby the multipotency of the cells is expanded over several population doublings.

Mesenchymal cells are traditionally grown on a fibroblast feeder layer that provides them with the necessary chemical signals to remain undifferentiated and to continue dividing over and over. After expansion these cells retain their ability to differentiate into a variety of mature cell types.

It had been thought previously that stem cells are directly influenced by cells in the local environment or ‘niche’, but Canadian researchers have recently (July 2007) published groundbreaking findings in the prestigious journal Nature that human embryonic stem cells can actually produce distinctive niche cells in vitro, which then release stem cell nourishing proteins to help keep their ‘parents’ ticking over.

Researchers understandably are interested in the relationship between stem cells and their niche, because the niche represents a route for modifying stem cell behavior. If human stem cells can be reliably guided down a particular pathway, then they can be more readily used for future clinical therapy to regenerate damaged tissue such as neurons for Parkinson’s disease, or insulin producing cells for diabetes.

Expansion Expansion refers to the proliferation capacity and the cell population doublings during a particular culture period. Undifferentiated Embryonic Stem cells have the potential for unlimited expansion in culture with retention of an ability to generate cells of all three germ layers - endoderm, mesoderm, and ectoderm. The early germ layer cells can then further differentiate into many specific cell lineages.

Umbilical cord blood (and adipose tissue) are attractive alternatives to bone marrow in isolating mesenchymal cells. Cord blood MSCs particularly seems to be expandable to higher numbers, meaning they can be cultured longest with the highest proliferation capacity(2). Optimised culture conditions resulted in more than 50 population doublings of umbilical cord mesenchymal cells after 15 weeks. Importantly, a clinical quantity of 100 million mesenchymal stromal cells with retained differentiation potential could be obtained from umbilical cord MSCs within approximately 7 weeks (3).

Cryopreservation After the clinically desired numbers of cells are cultured, standard cryogenic protocols are used for stem cell storage. During storage, it is critically important that stem cells maintain their undifferentiated status.

Regenerative Medicine The essential aim of regenerative medicine is to obtain adequate specific cell types or tissue to restore the normal physiology of a part of the body damaged by injury or disease.

Transplantation

Matched tissue For bone marrow transplantation as treatment for certain haematological diseases, matched tissue is required. In the general population the odds of finding someone with matching stem cells is thought to be one in 100 000, while 25% of siblings have matching tissue types. Globally there is a shortfall of matched bone marrow, and this is propelling the research towards improving the engraftment of umbilical cord blood.

Autograft For transplantation, the ideal in ensuring graft compatibility is to be able to take cells from the individual requiring treatment. This may occur either directly or following a period of growth and differentiation in vitro.

Allograft There is a considerable risk of graft incompatibility and a very real chance of immunorejection when cells or tissue are transplanted from an allogeneic source – i.e. source of independent origin / other than the patient.

Rejection Reports that transplanted umbilical cord mesenchymal cells do not precipitate an immunorejection reaction (4) (and may in fact suppress ongoing immune cell induced reactions in humans) offer much promise to those folk who are exploring stem cell therapy of this nature.

References 1. www.stemcell.com 2. Kern et al. Stem Cells 2006, 24(5): 1294-301 3. Reinisch et al. Regenerative Medicine 2007, 2(4):371-382 4. Can & Karahuseyinoglu Stem Cells Aug, 2007 epub

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