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Genetic and cellular aspects of the establishment of histocompatible stem cells: information gained from an animal model.

Lim JM, Gong SP - BMC Proc (2011)

Bottom Line: As an initial step, we succeeded in establishing histocompatible stem cells using preantral follicle cultures and subsequent parthenogenetic activation.However, more progress regarding the establishment and elucidation on origination of established cell lines is necessary to use this genetic manipulation-free procedure.Nevertheless, relevant information on the process will help to stimulate preclinical research on cell transformation into differentiated, undifferentiated, and even cancerous cells, as well as clinical studies on the application of induced pluripotent cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: WCU Biomodulation Program, Seoul National University, Seoul 151-742, Korea. limjm@snu.ac.kr.

ABSTRACT
The establishment of patient-specific histocompatible stem cells may be an alternative for overcoming current limitations in stem cell engineering. We are developing an animal model to assist the establishment of histocompatible, autologous stem cells. In this process, we obtained valuable information on establishing and characterizing stem cells. As an initial step, we succeeded in establishing histocompatible stem cells using preantral follicle cultures and subsequent parthenogenetic activation. The gene expression profile of the established stem cells was similar to that of embryonic stem cells (ESCs) derived from normal fertilization. On the other hand, we propose a way to derive histocompatible, ESC-like cells by co-culturing ovarian stromal cells with feeder fibroblasts, which may allow the derivation of stem cells from somatic tissue. However, more progress regarding the establishment and elucidation on origination of established cell lines is necessary to use this genetic manipulation-free procedure. Nevertheless, relevant information on the process will help to stimulate preclinical research on cell transformation into differentiated, undifferentiated, and even cancerous cells, as well as clinical studies on the application of induced pluripotent cells.

No MeSH data available.


Related in: MedlinePlus

Comparison of the gene expression profiles of embryonic stem cells (ESCs) derived from different origins. Two sets (A and B) of comparisons were made using two lines of parthenogenetic ESCs (pESC-1 and pESC-2 for A and B, respectively). In each set, the gene expression profile of normally fertilized ESCs (nfESCs) derived from R1 strain was first compared with the profile of nfESCs derived from B6D2F1 strain. Comparisons were subsequently made between pESCs and nfESCs of the same strain (B6D2F1) and between pESCs and nfESCs of a different strain (R1). In the first comparison (A), the change in gene expression after parthenogenesis was less than the change attributable to the strain difference; the number of genes with altered expression was similar among all comparisons in the second set (B). (Reprinted with permission from Gong et al., Hum Reprod 2009; 24: 815-814).
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Figure 1: Comparison of the gene expression profiles of embryonic stem cells (ESCs) derived from different origins. Two sets (A and B) of comparisons were made using two lines of parthenogenetic ESCs (pESC-1 and pESC-2 for A and B, respectively). In each set, the gene expression profile of normally fertilized ESCs (nfESCs) derived from R1 strain was first compared with the profile of nfESCs derived from B6D2F1 strain. Comparisons were subsequently made between pESCs and nfESCs of the same strain (B6D2F1) and between pESCs and nfESCs of a different strain (R1). In the first comparison (A), the change in gene expression after parthenogenesis was less than the change attributable to the strain difference; the number of genes with altered expression was similar among all comparisons in the second set (B). (Reprinted with permission from Gong et al., Hum Reprod 2009; 24: 815-814).

Mentions: A number of stem cell lines have been derived from follicle cultures, and the original system has been optimized by adding or deleting specific factors. To assess the clinical usefulness of our technology, it was important to determine whether the parthenogenetic stem cells had a potential for self-renewal and differentiation as well as physiological and genetic properties that were similar to those of normally fertilized stem cells or reported ESCs. The gene expression profiles of two parthenogenetic ESC lines were compared with those of two normally fertilized ESC lines using genome-wide microarray analysis [18]. The mRNA expression levels were quantified to validate the data. As shown in Fig 1, in two comparisons, i.e., one for each parthenogenetic ESC line, the reactions of 11,347 and 15,454 gene probes, respectively, were altered by parthenogenesis, while strain differences accounted for changes in the reactions of 15,750 and 14,944 probes. The correlation coefficient was higher for the comparisons between normally fertilized and parthenogenetic ESCs than for the comparisons between strains of normally fertilized ESCs. The expression levels of approximately 3,300 genes were changed after parthenogenesis, and about 90% of the major functional genes differentially expressed in one comparison set showed the same difference in the other comparison. The expression levels of several paternally and maternally imprinted genes were also altered after parthenogenesis, and the differentially expressed genes were similar for each comparison. Thus, although altered expression of some genes was observed in ESCs after parthenogenesis, the degree of alteration was similar to or less than that observed between ESC strains of the same derivation in a given genetic environment. Further information on cell differentiation and genetic stability in vivo after transplantation, as well as in vitro, is needed to confirm the clinical feasibility of our system.


Genetic and cellular aspects of the establishment of histocompatible stem cells: information gained from an animal model.

Lim JM, Gong SP - BMC Proc (2011)

Comparison of the gene expression profiles of embryonic stem cells (ESCs) derived from different origins. Two sets (A and B) of comparisons were made using two lines of parthenogenetic ESCs (pESC-1 and pESC-2 for A and B, respectively). In each set, the gene expression profile of normally fertilized ESCs (nfESCs) derived from R1 strain was first compared with the profile of nfESCs derived from B6D2F1 strain. Comparisons were subsequently made between pESCs and nfESCs of the same strain (B6D2F1) and between pESCs and nfESCs of a different strain (R1). In the first comparison (A), the change in gene expression after parthenogenesis was less than the change attributable to the strain difference; the number of genes with altered expression was similar among all comparisons in the second set (B). (Reprinted with permission from Gong et al., Hum Reprod 2009; 24: 815-814).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108227&req=5

Figure 1: Comparison of the gene expression profiles of embryonic stem cells (ESCs) derived from different origins. Two sets (A and B) of comparisons were made using two lines of parthenogenetic ESCs (pESC-1 and pESC-2 for A and B, respectively). In each set, the gene expression profile of normally fertilized ESCs (nfESCs) derived from R1 strain was first compared with the profile of nfESCs derived from B6D2F1 strain. Comparisons were subsequently made between pESCs and nfESCs of the same strain (B6D2F1) and between pESCs and nfESCs of a different strain (R1). In the first comparison (A), the change in gene expression after parthenogenesis was less than the change attributable to the strain difference; the number of genes with altered expression was similar among all comparisons in the second set (B). (Reprinted with permission from Gong et al., Hum Reprod 2009; 24: 815-814).
Mentions: A number of stem cell lines have been derived from follicle cultures, and the original system has been optimized by adding or deleting specific factors. To assess the clinical usefulness of our technology, it was important to determine whether the parthenogenetic stem cells had a potential for self-renewal and differentiation as well as physiological and genetic properties that were similar to those of normally fertilized stem cells or reported ESCs. The gene expression profiles of two parthenogenetic ESC lines were compared with those of two normally fertilized ESC lines using genome-wide microarray analysis [18]. The mRNA expression levels were quantified to validate the data. As shown in Fig 1, in two comparisons, i.e., one for each parthenogenetic ESC line, the reactions of 11,347 and 15,454 gene probes, respectively, were altered by parthenogenesis, while strain differences accounted for changes in the reactions of 15,750 and 14,944 probes. The correlation coefficient was higher for the comparisons between normally fertilized and parthenogenetic ESCs than for the comparisons between strains of normally fertilized ESCs. The expression levels of approximately 3,300 genes were changed after parthenogenesis, and about 90% of the major functional genes differentially expressed in one comparison set showed the same difference in the other comparison. The expression levels of several paternally and maternally imprinted genes were also altered after parthenogenesis, and the differentially expressed genes were similar for each comparison. Thus, although altered expression of some genes was observed in ESCs after parthenogenesis, the degree of alteration was similar to or less than that observed between ESC strains of the same derivation in a given genetic environment. Further information on cell differentiation and genetic stability in vivo after transplantation, as well as in vitro, is needed to confirm the clinical feasibility of our system.

Bottom Line: As an initial step, we succeeded in establishing histocompatible stem cells using preantral follicle cultures and subsequent parthenogenetic activation.However, more progress regarding the establishment and elucidation on origination of established cell lines is necessary to use this genetic manipulation-free procedure.Nevertheless, relevant information on the process will help to stimulate preclinical research on cell transformation into differentiated, undifferentiated, and even cancerous cells, as well as clinical studies on the application of induced pluripotent cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: WCU Biomodulation Program, Seoul National University, Seoul 151-742, Korea. limjm@snu.ac.kr.

ABSTRACT
The establishment of patient-specific histocompatible stem cells may be an alternative for overcoming current limitations in stem cell engineering. We are developing an animal model to assist the establishment of histocompatible, autologous stem cells. In this process, we obtained valuable information on establishing and characterizing stem cells. As an initial step, we succeeded in establishing histocompatible stem cells using preantral follicle cultures and subsequent parthenogenetic activation. The gene expression profile of the established stem cells was similar to that of embryonic stem cells (ESCs) derived from normal fertilization. On the other hand, we propose a way to derive histocompatible, ESC-like cells by co-culturing ovarian stromal cells with feeder fibroblasts, which may allow the derivation of stem cells from somatic tissue. However, more progress regarding the establishment and elucidation on origination of established cell lines is necessary to use this genetic manipulation-free procedure. Nevertheless, relevant information on the process will help to stimulate preclinical research on cell transformation into differentiated, undifferentiated, and even cancerous cells, as well as clinical studies on the application of induced pluripotent cells.

No MeSH data available.


Related in: MedlinePlus