**7. Aldehyde dehydrogenase in regenerative medicine**

Until today, studies showed that BM ALDHbr populations may be useful in several cell therapy applications (Gentry*, et al.*, 2007)**.** According to this information, ALDHbr population

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

Aldehyde Dehydrogenase: Cancer and Stem Cells 21

Ability to form neurospheres and retained

Transplantation significantly ameliorated disease progression and extended life, but did

colonies, and ducts, when transplanted into

and endocrine lineages in the developing

Express basal epithelial and characteristic

multipotency

Mammary epithelium Myoepithelial, luminal epithelial and mixed

pancreas

cell markers

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

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

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

mammary fat pads.

prostate progenitor

Protects the cornea from oxidative damage

not rescue the animals.

Strong myogenic potential on IM transplantation

Contributed to both exocrine

**TISSUE OBTAINED FROM BENEFITS**

Fetal mouse brain Subventricular and subcortical zones of adult

Biopsies or primary explants of human skeletal

mouse brain

muscle

mice

Cadaveric

this perspective may intensively continue.


Rat embryonic neural tube

Central acinar/terminal duct

cells from peripheral acinar duct units of adult

human limbic tissue

**Table 1.** Different tissue repair models including human ALDHbr cells (Balber, 2011).

SCs and has several functions in these cells just as they possess in somatic cells.

properties and locations of ALDH-positive cells have started to be investigated.

Neural Tissue

Skeletal Muscle

Mammary Epithelium

Pancreatic Cells

Prostate Epithelium

Corneal Limbic Cells

**8. Conclusion** 

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

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 intravenously administration.

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

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

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 ischemia (Keller, 2009)**.** 


**Table 1.** Different tissue repair models including human ALDHbr cells (Balber, 2011).
