Concise Review: Aldehyde Dehydrogenase Bright Stem and Progenitor Cell Populations from Normal Tissues: Characteristics, Activities, and Emerging Uses in Regenerative Medicine

Significance Mechanisms that control physiologic hematopoietic stem-cell (HSC) self-renewal remain largely unknown. Inhibition of retinoic acid (RA) signaling in HSCs maintained their primitive phenotype and function, and promoted their self-renewal. Moreover, bone marrow stroma’s expression of the cytochrome P450 retinoid-inactivating enzyme, CYP26, allowed HSC self-renewal by maintaining an environment low in retinoids. Thus, HSCs appear to be intrinsically programmed to undergo RA-mediated differentiation unless prevented from doing so by bone marrow niche CYP26. Modulation of RA signaling also holds promise for clinical HSC expansion.

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“…1). As expected (1,2), the transcriptional level of ALDH1A1 was also highly upregulated in CD34 + CD38 − cells (Fig. 1).…”

Section: Resultssupporting

confidence: 81%

“…ALDH1 also is a marker for stem cells from most other tissues, and its expression decreases as stem cells differentiate (2). Although ALDH1's precise function in stem-cell biology is unclear, the major biologic function of the ALDH1 family appears to be the biosynthesis of retinoic acid (RA), the active metabolite of vitamin A (retinol) (3).…”

mentioning

confidence: 99%

Regulation of human hematopoietic stem cell self-renewal by the microenvironment’s control of retinoic acid signaling

Ghiaur

Yegnasubramanian

Perkins

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

125

114

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“…Several workers have now reported that ALDHbr cells have higher stem cell activity than ALDHdim cells bearing similar surface antigens associated with stem cell activity [18]. Retinoid mediated regulatory changes have recently been shown to alter the ability of CD34 + cells in the peripheral circulation of coronary artery disease patients to home to ischemic tissue [48], a finding consistent with the idea that retinoids produced by ALDH play an important role in controlling the ability of stem cells to respond to ischemic damage.…”

Section: Discussionmentioning

confidence: 64%

“…None of the other ALDH isozymes that generate retinoic acids were expressed by these cells. Expression of only one ALDH1 subfamily isozyme that can oxidize retinoids appears to be a general characteristic of ALDHbr cells isolated by sorting with the BAAA substrate [18]. Retinoid oxidizing ALDH isozymes have a large substrate passage that permits bulky aldehyde substrates like retinoids and BAAA access to the catalytic site, while isozymes that oxidize small metabolic aldehyde substrates exclude such bulky substrates [41].…”

Section: Discussionmentioning

confidence: 99%

“…Cell populations with high aldehyde dehydrogenase (ALDH) enzymatic activity (ALDHbr cells) sorted from cord blood [14,15] and bone marrow [16,17] are among the candidates therapies being investigated to treat cardiovascular diseases [18]. Autologous ALDHbr bone marrow cells have been used safely in clinical trials to treat adults with critical limb ischemia [19] and ischemic heart failure [20].…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of Action of Human Aldehyde Dehydrogenase Bright Cells in Therapy of Cardiovascular Diseases: Expression Analysis of Angiogenic Factors and Aldehyde Dehydrogenase Isozymes

White

Smith²,

Gentry³

et al. 2012

J Stem Cell Res Ther

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Human stem cell populations that express high aldehyde dehydrogenase activity [ALDHbr cells] have angiogenic activity in preclinical models and have been used safely to treat patients in early clinical trials. Bone marrow ALDHbr cells are being developed for therapeutic use in ischemic cardiovascular diseases. The mechanisms by which ALDHbr cells repair ischemic tissue are unknown, but available data suggest that angiogenic factors released by ALDHbr cells are involved. Gene expression studies were performed, and bone marrow ALDHbr cells were found to express 69 of 84 angiogenic factors tested. The 25 most highly expressed genes included soluble cytokines and growth factors, cytokine receptors, extracellular matrix proteins, and cell-cell signaling receptors. ALDHdim bone marrow cells that do not express high levels of ALDH and that have no angiogenic activity in preclinical models expressed a different group of genes. CD105 and Ephrin B4 transcripts were expressed about 65-fold more highly in ALDHbr than ALDHdim cells, and expression of these proteins was demonstrated in ALDHbr cells by flow cytometry. Expression analysis probing all 19 ALDH isozymes and immunofluorescence both demonstrated that ALDH1A1, an enzyme that can generate retinoic acids from retinaldehyde, was the ALDH isozyme most highly over

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Successful Isolation of Liver Progenitor Cells by Aldehyde Dehydrogenase Activity in Na"ve Mice

et al. 2012

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The role of progenitor cells in liver repair and fibrosis has been extensively described, but their purification remains a challenge, hampering their characterization and use in regenerative medicine. To address this issue, we developed an easy and reproducible liver progenitor cell (LPC) isolation strategy based on aldehyde dehydrogenase (ALDH) activity, a common feature shared by many progenitor cells. We demonstrate that a subset of nonparenchymal mouse liver cells displays high levels of ALDH activity, allowing the isolation of these cells by fluorescence‐activated cell sorting. Immunocytochemistry and qPCR analyses on freshly isolated ALDH+ cells reveal an enrichment in cells expressing liver stem cell markers such as EpCAM, CK19, CD133, and Sox9. In culture, the ALDH+ population can give rise to functional hepatocyte‐like cells as illustrated by albumin and urea secretion and cytochrome P450 activity. ALDH1A1 expression can be detected in canals of Hering and bile duct epithelial cells and is increased on liver injury. Finally, we showed that the isolation and differentiation toward hepatocyte‐like cells of LPCs with high ALDH activity is also successfully applicable to human liver samples. Conclusion: High ALDH activity is a feature of LPCs that can be taken advantage of to isolate these cells from untreated mouse as well as human liver tissues. This novel protocol is practically relevant, because it provides an easy and nontoxic method to isolate liver stem cells from normal tissue for potential therapeutic purposes. (HEPATOLOGY 2012)

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Concise Review: Aldehyde Dehydrogenase Bright Stem and Progenitor Cell Populations from Normal Tissues: Characteristics, Activities, and Emerging Uses in Regenerative Medicine

Cited by 102 publications

References 55 publications

Regulation of human hematopoietic stem cell self-renewal by the microenvironment’s control of retinoic acid signaling

Regulation of human hematopoietic stem cell self-renewal by the microenvironment’s control of retinoic acid signaling

Mechanisms of Action of Human Aldehyde Dehydrogenase Bright Cells in Therapy of Cardiovascular Diseases: Expression Analysis of Angiogenic Factors and Aldehyde Dehydrogenase Isozymes

Successful Isolation of Liver Progenitor Cells by Aldehyde Dehydrogenase Activity in Na"ve Mice

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