**8. Conclusion**

20 Dehydrogenases

may play an important role in regenerative medicine owing to RAs ALDH product (Balber, 2011). Retinoic acids could influence tissue repair by binding to transcription factors and regulating developmental programs, especially ALDH1A1 and ALDH3A1 of enzyme isoforms that produce RAs from oxidize retinaldehyde (Moreb, 2008). Therefore, ALDH1a1 and ALDH1A3 may influence cell activity and proliferation by controlling intracellular

The studies about value of ALDHbr cells in regenerative medicine were conducted by different researchers. The regenerative potential of ALDHbr cells obtained from different tissues were investigated in various disease models such as ischemic tissue damage hind

In the beginning of studies, ALDHbr cells were obtained from bone marrow and umbilical cord blood and normal peripheral blood (Sondergaard*, et al.*, 2010)**.** Multipotent mesenchymal progenitors and endothelial progenitor cells are concentrated in human ALDHbr populations. Because of potential progenitor and paracrine activities of ALDHbr cells, these cells especially obtained from bone marrow are important for tissue repair.

Manipulation of the graft to selectively concentrate or expand hematopoietic and/or neural stem cells prior to transplant may be a potential strategy in the future. UCBT using ALDH bright cells from the CB units have shown faster and higher engraftment in preliminary study and is being explored further (Prasad & Kurtzberg, 2010). One of these studies showed that human cord blood progenitors with high ALDH activity improve vascular density in a model of acute myocardial infarction. In this study, ALDHbr cells were homed to the infracted anterior surface of the heart, while ALDH-low cells were in the spleen after

Another study with animal model of hindlimb ischemia demonstrated that the isolated ALDHbr cells effectively restored blood flow to ischemic areas by mediation of local formation of new blood vessels with largeer diameter and increasing capillary density even

The reason for the restoration of tissue perfusion by ALDHbr cells were attempted to be explained with angiogenic properties of these cell groups. Angiogenic factors secreted by transplanted ALDHbr cells stimulate formation of new blood vessels at sites of ischemic injury (human cord blood progenitors with high ALDH activity improve vascular density in a model of acute myocardial infarction). Paracrine mechanisms of ALDHbr cells can protect endothelial cells from ischemic damage and respond to ischemic tissue damage (Balber,

Another exciting finding is that ALDHbr cells improve formation of new vessels and increase capillary density, while ALDHbr cells together with ALDH-low cells did not restore tissue perfusion at all. It is suggested that ALDH-low cells can inhibit the homing and/or angiogenic activity of ALDHbr cells. This situation showed the importance of isolating ALDHbr cells from bone marrow tissue for therapeutic uses (Balber, 2011). As a result, ALDHbr cells may be promising for patients with ischemic heart failure and critical limb

retinoid concentrations and play important roles in stem cell biology (Balber, 2011).

limb model, brain damage and pancreatitis (Balber, 2011).

if there was no improvement in cardiac functions (Keller, 2009).

intravenously administration.

2011, White*, et al.*, 2011).

ischemia (Keller, 2009)**.** 

Since ALDH enzyme has been proven to possess a vital role in somatic cells and their deficiency cause various diseases, research has focused on the presence and functions of the enzyme in SCs. It was demonstrated that ALDH is an important marker for identification of SCs and has several functions in these cells just as they possess in somatic cells.

Exploring some of the isoforms of ALDH for use as a marker of CSCs improved the importance of ALDH. Thus, there are several methods to detect ALDHs and their levels (Marcato*, et al.*, 2011). After the discovery of ALDH activity in human and mouse bone marrow hematopoietic progenitor cells (HPCs) by Jones et al. (Jones*, et al.*, 1995), the properties and locations of ALDH-positive cells have started to be investigated.

Recently, ALDHbr cells were found in cancer tissues including breast, liver, colon, and acute myelogenous leukemia. It was demonstrated that proliferation rates, migration and adhesion ability, and metastatic potential of ALDHbr CSCs were more than ALDH low cells and ALDHbr cells related with cancer chemo resistance. ALDHbr cells became one of new therapeutic target against cancer and anti-cancer studies based on targeting ALDHbr cells have started recently (Serrano*, et al.*, 2011). It is expected that the anti-cancer studies with this perspective may intensively continue.

On the other hand, studies showed that BM ALDHbr populations may be useful in several cell therapy applications (Gentry*, et al.*, 2007). It is suggested that ALDHbr population may play an important role in regenerative medicine owing to Ras, which are one of the ALDH products. Paracrine effects of products of ALDH activity may influence tissue repair by binding to transcription factors and regulating developmental programs (Balber, 2011).

Aldehyde Dehydrogenase: Cancer and Stem Cells 23

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Therefore, regenerative potential of ALDHbr SCs were investigated in various disease models such as ischemic tissue damage hind limb model, brain damage and pancreatitis (Balber, 2011).

Studies on ALDHbr cells provide restoration of tissue perfusion and stimulation of formation of new blood vessels in ischemic tissue damage (Keller, 2009). These promising findings showed that ALDHbr cells may gain importance in different areas; however, there are still many things to investigate about potential properties of ALDHbr cells for use in regenerative medicine. Thus, ALDH have many roles such as a marker of many disease and cell lines for detection of them also can using for therapy and have potential for use in regenerative medicine.

However, there are few studies about ALDH as a marker of SCs and potential usage in regenerative medicine. Therefore, we suggested that studies should focus on this and this review aims to consider the roles of ALDH in SCs and their potential use in regenerative medicine. We believe that constructing a review including current studies related to this subject will guide future studies.
