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Stem cells, progenitors & regenerative medicine: A retrospection.

Bhartiya D - Indian J. Med. Res. (2015)

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Biology Department, National Institute for Research in Reproductive Health (ICMR), Mumbai 400 012, Maharashtra, India.

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It is well evident that the embryonic stem cells (ESCs) are pluripotent, can differentiate into all the three germ layers namely ectoderm, mesoderm and endoderm and into 200 odd cell types present in the body, are immortal, can expand in large numbers in vitro, and are genetically stable over long periods in culture... Differentiation of human ES cells into fully committed cell types in vitro is an inefficient process, thus attempts are made to transplant progenitors and allow in situ maturation... However, such efforts have resulted in short-term benefits... These stem cells have the potential to differentiate into various cell types in vitro but whether these can sustain long-term regeneration in situ remains to be demonstrated... Ting et al have found that the endocytic protein Ap2a2 possibly regulates asymmetric cell renewal of HSCs since it enhances HSC function without any substantial increase in HSC numbers and that the protein was asymmetrically distributed during cell division... However, more work needs to be done to prove this conclusively... However, the scientific community at large is not yet convinced by the existence of VSELs... This has resulted mainly because of their very small size and tendency to get discarded as debris during processing since these cells do not easily settle down on centrifugation... MSCs derived from adult bone marrow are considered to be pluripotent and several studies show their ability to trans-differentiate into all three germ layers... Against this backdrop, presence of pluripotent VSELs in various adult body organs needs to be accepted as (i) these have the ability to self-renew and differentiate into various cell types, (ii) their presence can explain asymmetric cell division and (iii) these could be the elusive cancer initiating cells as nuclear OCT-4 has now been reported in several cancers (Fig. 1; Table)... Most perplexing is the observation in our laboratory that VSELs are mobilized and increased in numbers (more than 5-folds based on flow cytometry studies) in a streptozotocin treated mouse pancreas (unpublished observation)... Then why these stem cells do not regenerate the diabetic pancreas? It is not easy to decipher well kept secrets of Mother Nature... To conclude, there is a huge scope for basic research in the field of stem cells biology before translating from the bench to bedside.

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Basic understanding on stem cells and progenitors.
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Figure 2: Basic understanding on stem cells and progenitors.

Mentions: Ratajczak's group has shown that total body irradiation completely destroys the HSCs in mice whereas the VSELs survive and have the ability to proliferate as evident from BrdU uptake46. Similarly, we have observed that chemotherapy destroys actively dividing germ cells in both ovary and testis; however, the VSELs persist in the gonads4748. These results suggest that VSELs are relatively quiescent (dormant) stem cells in the body organs whereas the HSCs, OGSCs (ovarian germ stem cells) and SSCs are the actively dividing (restless) progenitors that arise from the VSELs. Then what are the adult stem cells? The existing terminology appears to be a misnomer! The adult body organs harbour nuclear OCT-4 positive, relatively quiescent VSELs that resist oncotherapy and actively dividing progenitors with cytoplasmic OCT-4. The progenitors are tissue specific and differ based on their location (somatic microenvironment or the niche), in testis these are the SSCs, in ovary these are the OGSCs, in bone marrow HSCs whereas in the Wharton's jelly these are the MSCs. Thus the understanding based on differential expression of nuclear OCT-4 in VSELs and cytoplasmic OCT-4 in the progenitors has led to better understanding of stem cells biology49. We have also observed that under normal conditions it is the cytoplasmic OCT-4 positive progenitors that expand in number to maintain tissue homeostasis whereas uncontrolled expansion of nuclear OCT-4 positive VSELs results in testicular tumour50. To summarize, a confusion exists in the basic terminology of stem cells. Are adult stem cells indeed stem cells or just progenitors? As suggested earlier33, we believe that the term ASC is a misnomer, these are progenitors that arise from VSELs which are the true stem cells existing in various adult body organs (Fig. 2).


Stem cells, progenitors & regenerative medicine: A retrospection.

Bhartiya D - Indian J. Med. Res. (2015)

Basic understanding on stem cells and progenitors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4418150&req=5

Figure 2: Basic understanding on stem cells and progenitors.
Mentions: Ratajczak's group has shown that total body irradiation completely destroys the HSCs in mice whereas the VSELs survive and have the ability to proliferate as evident from BrdU uptake46. Similarly, we have observed that chemotherapy destroys actively dividing germ cells in both ovary and testis; however, the VSELs persist in the gonads4748. These results suggest that VSELs are relatively quiescent (dormant) stem cells in the body organs whereas the HSCs, OGSCs (ovarian germ stem cells) and SSCs are the actively dividing (restless) progenitors that arise from the VSELs. Then what are the adult stem cells? The existing terminology appears to be a misnomer! The adult body organs harbour nuclear OCT-4 positive, relatively quiescent VSELs that resist oncotherapy and actively dividing progenitors with cytoplasmic OCT-4. The progenitors are tissue specific and differ based on their location (somatic microenvironment or the niche), in testis these are the SSCs, in ovary these are the OGSCs, in bone marrow HSCs whereas in the Wharton's jelly these are the MSCs. Thus the understanding based on differential expression of nuclear OCT-4 in VSELs and cytoplasmic OCT-4 in the progenitors has led to better understanding of stem cells biology49. We have also observed that under normal conditions it is the cytoplasmic OCT-4 positive progenitors that expand in number to maintain tissue homeostasis whereas uncontrolled expansion of nuclear OCT-4 positive VSELs results in testicular tumour50. To summarize, a confusion exists in the basic terminology of stem cells. Are adult stem cells indeed stem cells or just progenitors? As suggested earlier33, we believe that the term ASC is a misnomer, these are progenitors that arise from VSELs which are the true stem cells existing in various adult body organs (Fig. 2).

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Biology Department, National Institute for Research in Reproductive Health (ICMR), Mumbai 400 012, Maharashtra, India.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

It is well evident that the embryonic stem cells (ESCs) are pluripotent, can differentiate into all the three germ layers namely ectoderm, mesoderm and endoderm and into 200 odd cell types present in the body, are immortal, can expand in large numbers in vitro, and are genetically stable over long periods in culture... Differentiation of human ES cells into fully committed cell types in vitro is an inefficient process, thus attempts are made to transplant progenitors and allow in situ maturation... However, such efforts have resulted in short-term benefits... These stem cells have the potential to differentiate into various cell types in vitro but whether these can sustain long-term regeneration in situ remains to be demonstrated... Ting et al have found that the endocytic protein Ap2a2 possibly regulates asymmetric cell renewal of HSCs since it enhances HSC function without any substantial increase in HSC numbers and that the protein was asymmetrically distributed during cell division... However, more work needs to be done to prove this conclusively... However, the scientific community at large is not yet convinced by the existence of VSELs... This has resulted mainly because of their very small size and tendency to get discarded as debris during processing since these cells do not easily settle down on centrifugation... MSCs derived from adult bone marrow are considered to be pluripotent and several studies show their ability to trans-differentiate into all three germ layers... Against this backdrop, presence of pluripotent VSELs in various adult body organs needs to be accepted as (i) these have the ability to self-renew and differentiate into various cell types, (ii) their presence can explain asymmetric cell division and (iii) these could be the elusive cancer initiating cells as nuclear OCT-4 has now been reported in several cancers (Fig. 1; Table)... Most perplexing is the observation in our laboratory that VSELs are mobilized and increased in numbers (more than 5-folds based on flow cytometry studies) in a streptozotocin treated mouse pancreas (unpublished observation)... Then why these stem cells do not regenerate the diabetic pancreas? It is not easy to decipher well kept secrets of Mother Nature... To conclude, there is a huge scope for basic research in the field of stem cells biology before translating from the bench to bedside.

No MeSH data available.