Clinical Applications of Novel Adult Stem Cell Derived Therapy

In 2001 a study was published claiming that stem cells derived from bone marrow could be used to repair damaged heart muscle following a severe cardiac event.33 This sparked a number of clinical studies involving intra-coronary injection of autologous bone-marrow-cells.34 The leap into clinical action has been criticized on several counts. Although, historically, drugs have been approved for general use without any knowledge of their mechanism of action, nowadays regulators prefer to see some...

Pancreatic stem cells

Endocrine pancreas, as well as the nervous system and heart, are organs with a very limited proliferative capacity compared to epidermis of the skin, intestinal epithelium, muscle, liver (after hepatectomy) and the very well studied bone marrow tissue (responsible for blood cell generation and osteoarticular turnover). Nevertheless, an interesting finding is that the tissues with no proliferation, such as the nervous system, bear progenitor stem cells. This is a key finding, because the...

Discussion

An attractive theoretical concept is to introduce the glucose sensing human insulin gene into stable autologous cells of the patient, so avoiding the need for immunosuppression, provided the immune target in the case of type I diabetes does not reside in these cells. The goal is similar to that outlined for the treatment of hemophilia A. Unanswered is the question, whether enough insulin could be produced at the right time for long enough to be of therapeutic use. These matters are likely to be...

Info

BFGF basic fibroblast growth factor EGF epidermal growth factor FBS fetal bovine serum KGF keratinocyte growth factor MEF* mitotically inactivated mouse embryonic fibroblasts neor neomycin resistance gene NIC nicotinamide. rat and human pancreatic islets.13 However, cell-lineage tracing strategies suggest that nestin-positive progenitors contribute to the formation of the microvasculature of the islet.14 The first protocol was developed by the group of McKay15 and comprised 5 stages 1)...

In vitro differentiation of MSCs

Cells are generally cultured in basal medium such as Dulbecco's modified Eagle's medium (high glucose) in the presence of 10 fetal bovine serum (FBS). The optimal expansion of MSCs from bone marrow requires the preselection of FBS.16'46 MSCs in culture have a fibroblastic morphology and adhere to the tissue culture substrate. Primary cultures are usually maintained for 12-16 days, during which time the nonadherent hematopoietic cell fraction is depleted. The addition of growth factor...

Biliary Epithelial Cells Rodent studies

When either massive damage is inflicted upon the liver or regeneration after damage is compromised, a potential stem cell compartment located within the smallest branches of the intrahepatic biliary tree is activated. This so-called oval cell or ductular reaction amplifies the biliary population before these cells differentiate into either hepatocytes or cholangiocytes.34-38 Careful studies in rats indicate that oval cells are predominantly derived from the canal of Hering, and thus this is the...

Sources of HSCs

There are three primary sources of hematopoietic stem cells for clinical use bone marrow, mobilized peripheral blood, and more recently, umbilical cord blood. Bone marrow Marrow is the traditional source of HSC for both allogeneic and autologous transplantation. Bone marrow is harvested by large bore needle aspiration from the donor's posterior ileac crests in the operating room, the donor being under general anesthesia. The harvest process generally requires 100-200 separate small volume...

Introduction

The liver is normally proliferatively quiescent, but hepatocyte loss through partial hepatectomy, uncomplicated by virus infection or inflammation, invokes a rapid regenerative response from all cell types in the liver to perfectly restore liver mass. Moreover, hepatocyte transplants in animals have shown that a certain proportion of hepatocytes in fetal and adult liver can clonally expand, suggesting that hepatoblasts hepatocytes are themselves the functional stem cells of the liver. More...

Other models

Fusion of bone marrow cells has also been found to occur in the normal mouse, not only with hepatocytes, but also with Purkinje cells and cardiomyocytes.78 These were very elegant studies in vivo and in vitro in which a reporter gene was activated only when cells fused. However, unlike the Fah null mouse, no selection pressure (liver damage) was operative, and even after 10 months only 9-59 fused cells 5.5 x 105 hepatocytes were found importantly, they also found evidence that with time either...

The Provenance of Stem Cells Does Source Matter

In spite of the fact that good scientific reasons can be supplied to support the claim that adult, ES and EG cell research should be carried out in parallel, ethical concerns over the provenance of the latter two cell types has resulted in outright bans or policy restrictions on their use, in many nations. Does the source of stem cells matter morally quite as much as people tend to think Embryonic germ (EG) cells are obtained by laboratory cultivation of primordial germ cells found in the fetal...

Inefficiencies of Cloning

It has been seven years since Dolly was born (Wilmut et al., 1997). In the most efficient treatment group, Wilmut et al. reported that 3.4 of embryos transferred resulted in live pregnancies using somatic cells as the donor. Since that time, despite intensive effort the efficiency of reproductive cloning in all species remains at approx. 5 (for recent review see Ref. 31). If we include the number of oocytes manipulated, the success falls to 1-2 ,8'32 an important consideration when discussing...

Microtubule and mitotic spindle defects in clones

The embryo formed during nuclear transfer must successfully complete many of the same functions during the first cell cycle that an embryo formed by normal fertilization must perform. While knowledge of the cytoplasmic events of the mammalian zygotic first cell cycle is far from complete, we do know a great deal about the necessary microtubule regulation during the first cell cycle of the fertilized zygote. Except for the mouse, all mammals studied41-46 adhere to the paternal inheritance of the...

Ocular Surface Disease Arising from Stem Cell Deficiency

Limbal stem cell deficiency can be caused by a variety of hereditary or acquired disorders.1'3 Possible inherited disorders in which limbal stem cells may be congenitally absent or dysfunctional are shown in Table 1. Limbal stem cells may also be deficient or destroyed by various acquired conditions. Acquired disorders form the majority of cases seen in the clinical setting. Limbal stem cell deficiency results in abnormal healing and epithelization of the cornea. It is characterized by...

The Tendon and Ligament Specific Progenitors and Differentiation Factors

Many of the recent studies have demonstrated that the bMSCs accelerate and improve tendon repair. However, these studies also verified that it is difficult to fully regenerate a tendon. The neo-tendons were similar to the native tendon but were not identical to the native tendon. This outcome may be due to two reasons. One is that the regeneration ability of tendon tissue is limited, unlike bone which can heal by regenerating normal bone in most instances, as an injured tendon often heal by...

Recent Progress in Recipient Immunosuppression

While the Edmonton immunosuppressive protocol represents a major step forward, the medications used in this protocol are associated with significant side effects that unfavorably alter the risk benefit ratio of islet transplantation. The therapy is currently unsuitable for the majority of patients with type 1 diabetes that are adequately stabilized on insulin. Approximately 10 of patients with type 1 diabetes, however, have severe forms of glycemic lability or recurrent hypoglycemia, and...

Cultural Persuasion

Grow cells in culture in the presence of differentiation factors that are known to be present in the embryonic development of the tissue in question. The sources of such cells could vary, for example A popular choice with the media attracted by the idea that ES cells can change into any cell type. To take an ESC all the way to a cell may involve numerous changing differentiation environments in normal development, probably influenced by what is going on in adjacent tissues. Currently, we have...

References

WolpertL, Hicklin J, HornbruchA. (1971) Positional information and pattern regulation in regeneration of hydra. Symp Soc Exp Biol 25 391-415. 2. Brockes JP. (1997) Amphibian limb regeneration Rebuilding a complex structure. Science 276 81-87. 3. Kiessling AA, Anderson SC. (2003) Human embryonic stem cells. Boston Jones and Bartlett. 4. Anderson DJ, Gage FH, Weissman IL. (2001) Can stem cells cross lineage boundaries Nature 7 393-395. 5. Bongso A, Richards M. (2004) History and perspective of...

The Edmonton Protocol

A new protocol was developed in Edmonton, Canada in 1999 that radically changed the face of clinical islet transplantation. The first seven patients treated under the Edmonton Protocol all achieved and maintained insulin independence beyond one year, demonstrating for the first time that islet transplantation could achieve insulin independence with rates similar to whole pancreas transplantation, but without a need for a major inter-ventional surgery.32 The success of this protocol has been...