Stem cells have been recognized for a number of years as bodies that are capable of division in such a way as to facilitate both the generation of differentiated cells and retention of the capacity to divide again without differentiation. In the most simple case a stem cell may divide asymmetrically and one of the progeny will remain as a stem cell and the other, often with considerable numbers of cell divisions on the way, will generate a specifically differentiated cell array. It is believed that the capacity of the human body to regenerate and repair itself in both normal and pathological circumstances can depend upon the activities of stem cells and, in recent years, much work has gone into their characterisation, provenance and definition of how they can be deployed to improve health.
Much of the original concept of stem cells derived from work on haematopoietic cell performance, often after injection of bone marrow into animals in which irradiation had been used to reduce or even ablate existing haematopoietic function. From this work it emerged that there were differing degrees of phyloprogenicity among adult stem cells displayed, in this instance, as initiators of haematopoiesis. It was also shown that foetal cells had, not surprisingly a more powerful stem cell potential in that they could quite easily outgrow adult stem cells in circumstances of demand for blood forming cells.
Since these early days work has tended to focus on embryonic stem cells not only for their demonstrably greater phyloprogenicity but also, following what seems a common sense belief, that they would have a greater flexibility to create more diverse pathways of differentiation.
The assumption, for which there is considerable evidence, is that, although most studies of the stem cell potential of bone marrow had concentrated on display of haematopoietic activity, bone marrow was also a source of multipotential cells that could, in circumstances not yet well defined, participate in the regeneration of many if not all organs of the body.
The fact that, in most if not all organs of the body, when regeneration or repair occurs recruitment is from locally available stem cells. It is not known whether such cells are multipotential or committed to particular pathways of development.
These concepts underline much contemporary work on stem cells.
There are practical problems in the way of deployment of embryonic stem cells, the most serious being, in the outbred human organism, that with some interesting exceptions transfer of embryonic stem cells would of necessity constitute an allograft and therefore be susceptible to immunological rejection. This in itself does not raise impossible difficulties as many allografted organs are functioning perfectly successfully under the umbrella of immunosuppression but it does create a problem that may be unnecessary. The demonstration, in a limited number of patients with Parkinson’s disease, that injection of foetal neuroembryoblasts into the corpora striata (in which it is believed there is a deficiency of functional cells arising from a chronic process of neurodegeneration) can lead to significant improvement in clinical status emphasises the possibilities. The brain is an immunologically privileged site which probably contributed to the success in the Parkinson’s disease cases. Unfortunately there are major logistic problems in getting enough human foetal cells to get a successful therapeutic outcome aside from the major ethical problems concerning the wider use of early human embryonic material.
In addition to the very considerable work presently being undertaken on embryonic stem cells much effort is going into amplification of stem cell numbers by their forced proliferation in vitro. This very promising approach carries with it the possibility that the cells concerned will undergo mutational changes leading to expression of malignant behaviour. Certainly in relation to some attempts to restore immunological function to children lacking it there have been indications that such an eventuality must be guarded against. In this respect it should be noted that there are a number of genetic devices that can be activated to destroy populations of transferred cells if they prove to exercise unwanted properties.
A totally different approach has been adopted by the OMNICYTE team. They have built on the finding that stem cells often if not always express a particular defined antigen codified as CD34+. CD34+ cells are present in normal adult blood but their number can be much augmented by prior injection of granulocyte colony-stimulating factor (GCSF).
GCSF is a glycoprotein, growth factor or cytokine produced by a number of different "Tissue (biology)" tissues to stimulate the bone marrow to produce granulocytes. It also stimulates the survival, proliferation, differentiation, and function of neutrophil granulocyte progenitor cells and mature neutrophils. The natural human glycoprotein exists in two forms of a 174- and 180- amino-acid-long protein of molecular weight 19,600 grams per mole. The more-abundant and more-active 174-amino acid form has been used in the development of pharmaceutical products by recombinant DNA (rDNA) technology. The point to be made here is that GCSF is available as an approved biopharmaceutical.
It has proved possible in many instances to use the white cell populations extracted from the blood of GCSF injected patients instead of bone marrow injections to replace bone marrow damaged by irradiation or radiomimetic chemicals. Thus we know with certainty that there are many stem cells in the blood of GCSF treated human patients.
The OMNICYTE team has gone further in extracting by immunofiltration of CD34+ cells from the blood of GCSF treated patients and believes that they can in this way produce highly purified stem cells that ex hypothesi are multipotent. These cells they have named OMNICYTES.
Much research is presently being undertaken to determine the surface properties of omnicytes, their plasticity in terms of capacity to express in vitro characteristics of differentiated cells perhaps indicating a capacity to develop along particular pathways of development. For example it has been shown that under certain circumstances omnicytes can express the properties of cells from the pancreas in their capability to synthesize insulin.
1A possible exception is the nervous system in relation to which there is presently no direct evidence that blood borne stem cells can effect its regeneration.