The Use of Adult Stem Cells in the Treatment of Diabetes By Joseph Chidiac

β-cell Progenitors In the recent past, scientists tried to determine whether β-cell progenitors exist in the human pancreas. Studies on rat models have indicated that some form of endocrine progenitor with the ability to differentiate into β-cells exist in the adult pancreas (Soria et al. 2005). During tests run on human samples run to determine the effect of SCs on β-cell development, it was found that new β-cells normally arise from preexisting ones (Dor et al. 2004).

The Role of Stem Cells Dor et al. noted that β-cells can proliferate in vivo, causing doubt that adult stem cells had a significant role in β-cell replenishment. Seaberg et al. then announced the discovery of multipotent progenitor cells that could differentiate into α-, β-, and δ-cells as well as exocrine, neural, and glial cells.

Location of Pancreatic Progenitors Pancreatic stem/precursor cells have been found to exist in the pancreatic ductal lining and are subject to activation in the case of injury, which increases β-cell mass through differentiation and proliferation (Xu et al. 2008).

Elusiveness of Pancreatic SCs Reports have identified pancreatic “stem” cells found in pancreatic islets (Guz et al. 2001), pancreatic ducts (Xu et al. 2008), as well as in random pancreatic areas (Seaberg et al. 2004). All stem/progenitor candidates are present at a rate of 1 cell per 3,000-9,000 pancreatic cells (Seaberg et al. 2004). One additional problem is that no consensus on the cell markers needed to definitively identify these progenitors has been made (Trucco et al. 2005).

Pancreatic “Side Populations” New research has found that the side population cells have stem cell properties and can be identified using the Pdx1 and CD326 cell surface markers (Banakh et al. 2012). These cells have been shown to have the ability to induce differentiation and proliferation of β-cells in the case of damage to the existing population (Banakh et al. 2012). They accomplish this by forming new islets that produce insulin in response to glucose (Banakh et al. 2012).

Replenishment with β-cells Restoring functional β-cells in diabetes by β-cell transplantation or in vivo β-cell stimulation for regeneration seem to be promising approaches (Houbracken et al. 2012). This, however, required an in depth knowledge of the mechanisms of β-cell neogenesis, which remains a controversial topic in regenerative medicine (Houbracken et al. 2012).

Possibilities β-cells might be regenerated by: Differentiation of endogenous stem cells. Proliferation of existing β-cells. A combination of both approaches.

Alternate Sources of Stem Cells It has been reported that SCs identified in the liver, spleen, CNS, and BM have the ability to differentiate into insulin-producing cells (Zulewski et al. 2006). There is also the option of using iPSCs reprogrammed from a number of cells found in various tissues (Park et al. 2008).

iPSCs for Diabetes Tests have been performed to determine the rate of differentiation of iPSCs (achieved by reprogramming a patient’s own somatic cells) into insulin-producing cells (Thatava et al. 2012). Successful generation of insulin-producing cells seems to depend on the silencing of stem-ness pathways and the induction of certain pancreatic transcription factors (Thatava et al. 2012).

hPSCs and hESCs Both human pluripotent and embryonic stem cells have been successfully differentiated into insulin-producing cells, but these cells are ultimately polyhormonal and non-functional (Nostro et al. 2012). However, β-cells derived from hESCs have been shown to be fully functional in immuno-suppressed mice (Nostro et al. 2012). Meanwhile, our understanding of the factors affecting β-cell differentiation from iPSCs and their homeostasis is advancing rapidly (Raducanu et al. 2012).

HSC Transplantation It is true that Hematopoietic SCs have the ability to differentiate into pancreatic β-cells. However, transplantation into the pancreas for the treatment of diabetes is followed by extreme hyperglycemia, which is indicative of graft versus host disease or GVHD (Gebremedhin et al. 2012).

In Summation Treating type 1 & 2 diabetes using stem cell therapy will undoubtedly require using one of the more successful strategies (ESCs and iPSCs) while taking into account the need for β-cell replenishment as well as the need to suppress an aggressive immune response to insulin-producing cells (Stanekzai et al. 2012). Next let us explore the use of ESCs in the treatment of diabetes.