scholarly journals Human Adipose Tissue Is a Source of Multipotent Stem Cells

2002 ◽  
Vol 13 (12) ◽  
pp. 4279-4295 ◽  
Author(s):  
Patricia A. Zuk ◽  
Min Zhu ◽  
Peter Ashjian ◽  
Daniel A. De Ugarte ◽  
Jerry I. Huang ◽  
...  

Much of the work conducted on adult stem cells has focused on mesenchymal stem cells (MSCs) found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. Preliminary studies have recently identified a putative stem cell population within the adipose stromal compartment. This cell population, termed processed lipoaspirate (PLA) cells, can be isolated from human lipoaspirates and, like MSCs, differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches. PLA cells expressed multiple CD marker antigens similar to those observed on MSCs. Mesodermal lineage induction of PLA cells and clones resulted in the expression of multiple lineage-specific genes and proteins. Furthermore, biochemical analysis also confirmed lineage-specific activity. In addition to mesodermal capacity, PLA cells and clones differentiated into putative neurogenic cells, exhibiting a neuronal-like morphology and expressing several proteins consistent with the neuronal phenotype. Finally, PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression.

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Rhian Stavely ◽  
Ainsley M. Robinson ◽  
Sarah Miller ◽  
Richard Boyd ◽  
Samy Sakkal ◽  
...  

2010 ◽  
Vol 16 (2) ◽  
pp. 523-533 ◽  
Author(s):  
Brian O. Diekman ◽  
Christopher R. Rowland ◽  
Donald P. Lennon ◽  
Arnold I. Caplan ◽  
Farshid Guilak

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3596-3606 ◽  
Author(s):  
Troy D. Randall ◽  
Irving L. Weissman

Abstract A significant fraction of hematopoietic stem cells (HSCs) have been shown to be resistant to the effects of cytotoxic agents such as 5-fluorouracil (5-FU), which is thought to eliminate many of the rapidly dividing, more committed progenitors in the bone marrow and to provide a relatively enriched population of the most primitive hematopoietic progenitor cells. Although differences between 5-FU–enriched progenitor populations and those from normal bone marrow have been described, it remained unclear if these differences reflected characteristics of the most primitive stem cells that were revealed by 5-FU, or if there were changes in the stem-cell population itself. Here, we have examined some of the properties of the stem cells in the bone marrow before and after 5-FU treatment and have defined several activation-related changes in the stem-cell population. We found that long-term reconstituting stem cells decrease their expression of the growth factor receptor c-kit by 10-fold and increase their expression of the integrin Mac-1 (CD11b). These changes begin as early as 24 hours after 5-FU treatment and are most pronounced within 2 to 3 days. This activated phenotype of HSCs isolated from 5-FU–treated mice is similar to the phenotype of stem cells found in the fetal liver and to the phenotype of transiently repopulating progenitors in normal bone marrow. We found that cell cycle is induced concomitantly with these physical changes, and within 2 days as many as 29% of the stem-cell population is in the S/G2/M phases of the cell cycle. Furthermore, when examined at a clonal level, we found that 5-FU did not appear to eliminate many of the transient, multipotent progenitors from the bone marrow that were found to be copurified with long-term repopulating, activated stem cells. These results demonstrate the sensitivity of the hematopoietic system to changes in its homeostasis and correlate the expression of several important surface molecules with the activation state of HSCs.


Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3210-3217
Author(s):  
Chiann-Chyi Chen ◽  
Amariliz Rivera ◽  
Naomi Ron ◽  
Natalie Sutkowski ◽  
Joseph P. Dougherty ◽  
...  

The current paradigm concerning the kinetics of hematopoiesis is that only the most primitive pluripotential bone marrow stem cells can support prolonged hematopoiesis whereas more differentiated, lineage-committed stem cells can only contribute to a particular lineage for a limited period of time. In this study, we present evidence that in mice, the spleen contains a long-lived myeloid-committed stem cell population(s) that continuously replenishes the mature myeloid lineage for at least 9 months. After myeloid-specific retroviral-mediated gene transfer, the exogenous gene could be detected in thioglycollate-induced macrophages and granulocytes by Southern blot analysis and by in situ polymerase chain reaction on an individual cell basis. The targeted stem cell population does not repopulate the bone marrow in secondary recipients and did not give rise to cells other than cells of the myeloid lineage. It therefore represents the first nonpluripotential stem cell population capable of replenishing a hemopoietic lineage for a long period of time. The ability to target a myeloid-specific stem cell could facilitate gene therapy of congenital disorders of the myeloid system such as lysosomal storage diseases. It also offers a unique opportunity to assess the immunologic consequences of expressing an exogenous gene of choice exclusively in the myeloid lineage. © 1998 by The American Society of Hematology.


Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3210-3217 ◽  
Author(s):  
Chiann-Chyi Chen ◽  
Amariliz Rivera ◽  
Naomi Ron ◽  
Natalie Sutkowski ◽  
Joseph P. Dougherty ◽  
...  

Abstract The current paradigm concerning the kinetics of hematopoiesis is that only the most primitive pluripotential bone marrow stem cells can support prolonged hematopoiesis whereas more differentiated, lineage-committed stem cells can only contribute to a particular lineage for a limited period of time. In this study, we present evidence that in mice, the spleen contains a long-lived myeloid-committed stem cell population(s) that continuously replenishes the mature myeloid lineage for at least 9 months. After myeloid-specific retroviral-mediated gene transfer, the exogenous gene could be detected in thioglycollate-induced macrophages and granulocytes by Southern blot analysis and by in situ polymerase chain reaction on an individual cell basis. The targeted stem cell population does not repopulate the bone marrow in secondary recipients and did not give rise to cells other than cells of the myeloid lineage. It therefore represents the first nonpluripotential stem cell population capable of replenishing a hemopoietic lineage for a long period of time. The ability to target a myeloid-specific stem cell could facilitate gene therapy of congenital disorders of the myeloid system such as lysosomal storage diseases. It also offers a unique opportunity to assess the immunologic consequences of expressing an exogenous gene of choice exclusively in the myeloid lineage. © 1998 by The American Society of Hematology.


Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1743-1751 ◽  
Author(s):  
Eun J. Gang ◽  
Darko Bosnakovski ◽  
Camila A. Figueiredo ◽  
Jan W. Visser ◽  
Rita C. R. Perlingeiro

Abstract Adult bone marrow (BM) contains hematopoietic stem cells (HSCs) as well as a nonhematopoietic, stromal cell population. Within this stromal population are mesenchymal stem cells (MSCs), which not only support hematopoiesis but also differentiate into multiple lineages, including fat, bone, and cartilage. Because of this multipotentiality, the MSC is an attractive candidate for clinical applications to repair or regenerate damaged tissues of mesenchymal origin. However, research progress has been hampered by the limited existing knowledge of the biology of these cells, particularly by the lack of a suitable marker for their prospective isolation. Here, we report that SSEA-4, an early embryonic glycolipid antigen commonly used as a marker for undifferentiated pluripotent human embryonic stem cells and cleavage to blastocyst stage embryos, also identifies the adult mesenchymal stem cell population.


2021 ◽  
Author(s):  
Zahra Eydian ◽  
Alaleh Mohammad Ghasemi ◽  
Samira Ansari ◽  
Ali Naghi Kamali ◽  
Maryam Khosravi ◽  
...  

Abstract Background: Mesenchymal stem cells (MSCs) from human adipose tissue and bone marrow have a great potential for use in cell therapy due to their ease of isolation, expansion, and differentiation. Our intention was to isolate and promote in vitro expansion and differentiation of MSCs from human adipose and bone marrow tissue into cells with a pancreatic endocrine phenotype and to compare the potency of these cells together.Methods and Results: MSCs were pre-induced with nicotinamide, mercaptoethanol, B-27 and b-FGF in L-DMEM for 2 days and re-induced again in supplemented H-DMEM for another 3 days. Expression of five genes in differentiated beta cells was evaluated by Real-time PCR and western blotting and the potency of insulin release in response to glucose stimulation was evaluated by insulin and C-peptide ELISA kit.Quantitative RT-PCR results showed up-regulation of four genes in differentiated beta-islet cells (Insulin, Ngn-3, Pax-4 and Pdx-1) compared with the control. Western blot analysis showed that MSCs cells mainly produced proinsulin and insulin after differentiation but nestin was more expressed in pre-differentiated stem cells. Glucose and insulin secretion assay showed that insulin levels and C-peptide secretion were significantly increased in response to 10 mM glucose.Conclusions: Our study showed that both adipose and bone marrow stem cells could differentiate into functional beta-islet cells but it seems that adipose stem cells could be a better choice for treatment of diabetes mellitus according to their more safety and potency.


Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3596-3606 ◽  
Author(s):  
Troy D. Randall ◽  
Irving L. Weissman

A significant fraction of hematopoietic stem cells (HSCs) have been shown to be resistant to the effects of cytotoxic agents such as 5-fluorouracil (5-FU), which is thought to eliminate many of the rapidly dividing, more committed progenitors in the bone marrow and to provide a relatively enriched population of the most primitive hematopoietic progenitor cells. Although differences between 5-FU–enriched progenitor populations and those from normal bone marrow have been described, it remained unclear if these differences reflected characteristics of the most primitive stem cells that were revealed by 5-FU, or if there were changes in the stem-cell population itself. Here, we have examined some of the properties of the stem cells in the bone marrow before and after 5-FU treatment and have defined several activation-related changes in the stem-cell population. We found that long-term reconstituting stem cells decrease their expression of the growth factor receptor c-kit by 10-fold and increase their expression of the integrin Mac-1 (CD11b). These changes begin as early as 24 hours after 5-FU treatment and are most pronounced within 2 to 3 days. This activated phenotype of HSCs isolated from 5-FU–treated mice is similar to the phenotype of stem cells found in the fetal liver and to the phenotype of transiently repopulating progenitors in normal bone marrow. We found that cell cycle is induced concomitantly with these physical changes, and within 2 days as many as 29% of the stem-cell population is in the S/G2/M phases of the cell cycle. Furthermore, when examined at a clonal level, we found that 5-FU did not appear to eliminate many of the transient, multipotent progenitors from the bone marrow that were found to be copurified with long-term repopulating, activated stem cells. These results demonstrate the sensitivity of the hematopoietic system to changes in its homeostasis and correlate the expression of several important surface molecules with the activation state of HSCs.


2020 ◽  
Author(s):  
Hongyu Zhang ◽  
Jiejuan Lai ◽  
Shifang Jiang ◽  
Ling Shuai ◽  
Yujun Zhang ◽  
...  

Abstract Background: We previously isolated a novel mesenchymal stem cell (MSC)-like neuroglial antigen 2-expressing stem cell population (MLpvNG2) from an uninjured liver by using a “Porcoll-Plate-Wait” method and determined that MLpvNG2 possesses hepatic stem/progenitor cell characteristics.Methods: In this study, we compared the biological and functional characteristics of the intrahepatic (MSC)-like MLpvNG2 with identical bone marrow-derived MSCs (niBM-MSCs), which are a well-accepted stem cell population in the field. We performed an in vitro study using conditioned medium and in vivo study using our well-set diethylnitrosamine (DEN)-induced liver fibrotic/cirrhotic murine model as well. Results: We found that in a fibrotic liver environment, MLpvNG2 survived better than niBM-MSCs obtained through different mechanisms of action. MLpvNG2 mainly differentiates into albumin (ALB(+)) hepatocytes, while niBM-MSCs mainly differentiate into CK/KRT19(+) cholangiocytes. Of note, we identified for the first time that C/EBPα/β is expressed on the cell surface of donor and host hepatic cells. As such, we used anti-C/EBPs neutralizing antibodies to determine the functional characteristics both in vitro (conditioned medium) and in the DEN-induced animal model.Conclusions: Based on our findings, it can be concluded that native-source (liver) stem cells (MLpvNG2) are more efficient than nonnative-sourced stem cells (niBM-MSCs) in the treatment of native (liver)-sourced diseases such as end-stage liver disease.


2005 ◽  
Vol 129 (1) ◽  
pp. 118-129 ◽  
Author(s):  
Benedicte Puissant ◽  
Corinne Barreau ◽  
Philippe Bourin ◽  
Cyril Clavel ◽  
Jill Corre ◽  
...  

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