Adult telomerase positive stem cells

Figure 1: Phase contrast micrograph of cultured cells: aTPSCs: TSCs (2), PSC (1), and partial MSC. Reprinted with permission from Young HE, Speight MO (2020). "Characterization of endogenous telomerase-positive stem cells for regenerative medicine, a review". Stem Cell and Regenerative Medicine. 4 (2): 1–14.[1]

Adult telomerase-positive stem cells (aTPSCs) are a proposed population of endogenous adult stem cells described in publications by Henry E. Young and collaborators. They are reported to reside in connective tissue stroma throughout life and to retain activity of the enzyme telomerase while in an undifferentiated state.[2][3][4]

History

The aTPSC model is attributed to work by Henry E. Young, who began studying tissue repair and regeneration in the 1970s in adult terrestrial salamanders, including Ambystoma annulatum.[5][6][7] Later publications proposed that the smallest aTPSCs, (TSCs, 0.1–2 μm), were seen as early as a 4-cell stage morula due to asymmetric division of the blastomeres, and with a similar differentiation potential (Figure 1).[4][8][9]

Endogenous aTPSCs have been reported in fifteen different animal species, including amphibians,[5][6][7] reptiles such as Komodo dragon,[10][11][12][13] avians such as chickens and wattled cranes[11][12][13][14], mice,[14][15][16] rats,[17][18][19][20][21][22][23] rabbits,[24] cats,[25] dogs,[10][25] sheep,[25] goats,[25] cows,[25] horses,[25][26] pigs,[27][28] spectacled bear,[10] and humans,[10][29][30][31][32] making them a conserved population of stem cells throughout phylogeny.

Proposed biological characteristics

According to published descriptions, undifferentiated aTPSCs retain telomerase activity and are therefore proposed to have prolonged proliferative capacity compared with telomerase-negative progenitor cells.[4] The model contrasts these cells with mesenchymal stem cells (MSCs), which are generally described as adult progenitor cells with limited in vitro expansion capacity.[33][34] The broader cellular-aging context includes the Hayflick limit, the observation that normal human diploid cells have a finite replicative lifespan in culture.[35][36] In the aTPSC model, cells are said to lose telomerase enzyme after lineage commitment and to acquire a finite replicative lifespan from that point. Consequently, their biologic clock resets to zero meaning the replacement tissues they generate are essentially biologically young relative to the age of the host.[2][4]

Proposed hierarchy

The literature describes aTPSCs as a continuum of eight subcategories distinguished by size, potency and surface-marker profile.[2][4]

Proposed aTPSC subcategories
SubcategoryApproximate sizeProposed potencyProposed forming capacity
Totipotent stem cells (TSCs)0.1–2.0 μmTotipotentSomatic cells, gametes and nucleus pulposus of the intervertebral disc
Halo-like stem cells (HLSCs)>2–4 μmTransitional pluripotentTransitional population between TSCs and PSCs
Corona-like stem cells (CLSCs)4–<6 μmTransitional pluripotentTransitional population between HLSCs and PSCs
Pluripotent stem cells (PSCs)6–8 μmPluripotentSomatic cells only
Germ-layer lineage stem cells (GLSCs)8–10 μmTransitionalBetween pluripotency and specialized lineages
Ectodermal stem cells (EctoSCs)10–12 μmLineage-specificEctodermal tissues
Mesodermal stem cells (MesoSCs)10–12 μmLineage-specificMesodermal tissues
Endodermal stem cells (EndoSCs)10–12 μmLineage-specificEndodermal tissues

Distribution and activation

According to the literature, aTPSCs occur in the interstitial connective tissue stroma of multiple organs and tissues, including skeletal muscle, bone marrow, heart, skin, kidney, spleen, peripheral blood, and brain.[27][37][38] They are described as quiescent under normal conditions and as capable of activation following trauma or chronic disease.[27] The proposed mechanism includes symmetric proliferation of maternal cells, release of daughter cells, migration to injured tissue by reverse diapedesis, and responses to local tissue-specific cues, including exosome-associated signals.[4][39][40]

Immunophenotype

The aTPSC literature describes each proposed subcategory as having a characteristic cluster of differentiation (CD) marker profile.[41]

Proposed immunophenotypic profiles
SubcategoryReported CD markersNotes
TSCsCD66e, CEA-CAM-1Described as lacking MHC class I
HLSCsCD66e high/CD10 low; CEA-CAM-1 high/SSEA-4 lowTransitional; described as lacking MHC class I
CLSCsCD66e low/CD10 high; CEA-CAM-1 low/SSEA-4 highTransitional; described as lacking MHC class I
PSCsCD10, SSEA-4Described as lacking MHC class I
GLSCsCD10 high/CD90 low; SSEA-4 high/Thy-1 lowDescribed as lacking MHC class I
EctoSCsCD56, CD90/Thy-1, MHC class IMHC class I reported
MesoSCsCD13, CD90/Thy-1, MHC class IMHC class I reported
EndoSCsCD90/Thy-1, MHC class IMHC class I reported

The absence of MHC class I on the more primitive proposed populations suggests that some aTPSC subcategories may have allogeneic applications, whereas lineage-specific cells expressing MHC class I would not be expected to share the same immunological profile.[2][4][41]

Therapeutic claims

There are published reports describing autologous and allogeneic use of telomerase-positive stem cells in chronic diseases and traumatic injuries, including osteoarthritis, systemic lupus erythematosus, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, celiac disease, cardiovascular disease, age-related macular degeneration, Alzheimer's disease, visual impairment, spinal-cord injury, chronic inflammatory demyelinating polyneuropathy and Parkinson disease.[10][42][43][44] The cited reports state that these studies involved 96 individuals and 20 chronic diseases or traumatic injuries, with a reported 100% safety record and cumulative efficacy of 86.4%. These figures should be treated as claims from the cited aTPSC literature rather than independently established clinical consensus.[10][42][43][44]

Controversy and criticism

Concerns have been raised about the reliability and reproducibility of the reported isolation protocols. The methods described by Young and collaborators differ from standard protocols used for differentiated cells, progenitor cells, MSCs, iPSCs and ESCs. Young has argued that aTPSCs constitute a distinct cell population and therefore require distinct processing and culture methods.[2][4]

See also

References

  1. ↑ Young HE, Speight MO (2020). "Characterization of endogenous telomerase-positive stem cells for regenerative medicine, a review". Stem Cell & Regenerative Medicine. 4 (2): 1–14. doi:10.33425/2639-9512.1047.
  2. 1 2 3 4 5 Young HE, Speight MO, Black AC (2017). "Functional cells, maintenance cells, and healing cells". Journal of Stem Cell Research. 1 (1): 1–41. doi:10.33425/2639-9512.1003. Article 003.
  3. ↑ Young HE (2023). "Healing cells: use what the Almighty created to heal thyself". American Journal of Medical and Clinical Research & Reviews. 2 (7): 1–19. doi:10.58372/2835-6276.1049.
  4. 1 2 3 4 5 6 7 8 Young HE, Speight MO (2020). "Characterization of endogenous telomerase-positive stem cells for regenerative medicine, a review". Stem Cells and Regenerative Medicine. 4 (2): 1–14. doi:10.33425/2639-9512.1047.
  5. 1 2 Young HE, Bailey CF, Dalley BK (1983). "Environmental conditions prerequisite for complete limb regeneration in the postmetamorphic adult land-phase salamander, Ambystoma". The Anatomical Record. 206: 289–294. doi:10.1002/ar.1092060307.
  6. 1 2 Young HE, Bailey CF, Markwald RR, Dalley BK (1985). "Histological analysis of limb regeneration in postmetamorphic adult Ambystoma". The Anatomical Record. 212: 183–194. doi:10.1002/ar.1092120210.
  7. 1 2 Young HE (2004). "Existence of reserve quiescent stem cells in adults, from amphibians to humans". Current Topics in Microbiology and Immunology. 280: 71–109. doi:10.1007/978-3-642-18846-6_2. PMID 14594209.
  8. ↑ Young HE, Black AC (2014). "Pluripotent stem cells, endogenous versus reprogrammed, a review". MOJ Orthopedics & Rheumatology. 1 (4). doi:10.15406/mojor.2014.01.00019. 00019.
  9. ↑ Young HE, Black AC Jr (2004). "Adult stem cells". The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology. 267A: 75–102. doi:10.1002/ar.a.20034. PMID 14699636.
  10. 1 2 3 4 5 6 Young HE, Speight MO (2020). "Osteoarthritis treated with telomerase-positive adult stem cells in animals and humans". Stem Cells and Regenerative Medicine. 4 (2): 1–11. doi:10.33425/2639-9512.1049.
  11. 1 2 Young HE, Morrison DC, Martin JD, Lucas PA (1991). "Cryopreservation of embryonic chick myogenic lineage-committed stem cells". Journal of Tissue Culture Methods. 13: 275–284. doi:10.1007/BF02388257.
  12. 1 2 Young HE, Sippel J, Putnam LS, Lucas PA, Morrison DC (1992). "Enzyme-linked immuno-culture assay". Journal of Tissue Culture Methods. 14: 31–36. doi:10.1007/BF01404544.
  13. 1 2 Young HE, Ceballos EM, Smith JC, Lucas PA, Morrison DC (1992). "Isolation of embryonic chick myosatellite and pluripotent stem cells". Journal of Tissue Culture Methods. 14: 85–92. doi:10.1007/BF01404612.
  14. 1 2 Young HE, Ceballos EM, Smith JC, Mancini ML, Wright RP, Ragan BL, Bushell I, Lucas PA (1993). "Pluripotent mesenchymal stem cells reside within avian connective tissue matrices". In Vitro Cellular & Developmental Biology. 29A: 723–736. doi:10.1007/BF02631429.
  15. ↑ Young HE, Mancini ML, Wright RP, Smith JC, Black AC Jr, Reagan CR, Lucas PA (1995). "Mesenchymal stem cells reside within the connective tissues of many organs". Developmental Dynamics. 202 (2): 137–144. doi:10.1002/aja.1002020205. PMID 7538011.
  16. ↑ Rogers JJ, Adkison LR, Black AC Jr, Lucas PA, Young HE (1995). "Differentiation factors induce expression of muscle, fat, cartilage, and bone in a clone of mouse pluripotent mesenchymal stem cells". The American Surgeon. 61 (3): 231–236. PMID 7887537.
  17. ↑ Lucas PA, Calcutt AF, Southerland SS, Wilson JA, Harvey RL, Warejcka D, Young HE (1995). "A population of cells resident within embryonic and newborn rat skeletal muscle is capable of differentiating into multiple mesodermal phenotypes". Wound Repair and Regeneration. 3 (4): 449–460. doi:10.1046/j.1524-475X.1995.30410.x. PMID 17147657.
  18. ↑ Warejcka DJ, Harvey R, Taylor BJ, Young HE, Lucas PA (1996). "A population of cells isolated from rat heart capable of differentiating into several mesodermal phenotypes". Journal of Surgical Research. 62 (2): 233–242. doi:10.1006/jsre.1996.0198. PMID 8632643.
  19. ↑ "Neuronal differentiation of stem cells isolated from adult muscle". Journal of Neuroscience Research. 69 (6): 894–907. 2002. doi:10.1002/jnr.10374. PMID 12205681.
  20. ↑ "Isolation and characterization of cells with neurogenic potential from adult skeletal muscle". Biochemical and Biophysical Research Communications. 317 (3): 893–901. 2004. doi:10.1016/j.bbrc.2004.03.121. PMID 15081424.
  21. ↑ Seruya M, Shah A, Pedrotty D, du Laney T, Melgiri R, McKee JA, Young HE, Niklason LE (2004). "Clonal population of adult stem cells: life span and differentiation potential". Cell Transplantation. 13 (2): 93–101. doi:10.3727/000000004773301753. PMID 15129757.
  22. ↑ Vourc'h P, Lacar B, Mignon L, Lucas PA, Young HE, Chesselet MF (2005). "Effect of neurturin on multipotent cells isolated from the adult skeletal muscle". Biochemical and Biophysical Research Communications. 332 (1): 215–223. doi:10.1016/j.bbrc.2005.04.116. PMID 15896319.
  23. ↑ Mignon L, Vourc'h P, Romero-Ramos M, Osztermann P, Young HE, Lucas PA, Chesselet MF (2005). "Transplantation of multipotent cells extracted from adult skeletal muscles into the subventricular zone of adult rats". Journal of Comparative Neurology. 491 (2): 96–108. doi:10.1002/cne.20707. PMID 16127691.
  24. ↑ Pate DW, Southerland SS, Grande DA, Young HE, Lucas PA (1993). "Isolation and differentiation of mesenchymal stem cells from rabbit muscle". Surgical Forum. 44: 587–589.
  25. 1 2 3 4 5 6 Young HE, Lochner F, Lochner D, McCommon G, Black AC Jr (2017). "Primitive stem cells in adult feline, canine, ovine, caprine, bovine, and equine peripheral blood". Journal of Stem Cell Research. 1 (1): 1–6. doi:10.4172/2161-0479.1000103.
  26. ↑ McCommon GW, Lochner F, Black AC Jr, Young HE (2013). "Primitive adult-derived stem cells are present in the blood of adult equines and can be increased in number with moderate exercise or ingestion of a cyanobacter, Aphanizomenon flos-aquae". Autacoids. 2 (1) 1000103. doi:10.4172/2161-0479.1000103.
  27. 1 2 3 Stout CL, Ashley DW, Morgan JH, Long GF, Collins JA, Limnios JI, et al. (2007). "Primitive stem cells reside in adult swine skeletal muscle and are mobilized into the peripheral blood following trauma". The American Surgeon. 73 (11): 1106–1110. doi:10.1177/000313480707301105.
  28. ↑ Young HE, Limnios JI, Lochner F, McCommon G, Black GF, Coleman JA, Hawkins KC, Black AC Jr (2017). "Healing cells in the dermis and adipose tissue of the adult pig". Journal of Stem Cell Research. 1 (2): 1–5. 004.
  29. ↑ "Adult stem cells: from bench-top to bedside". Tissue Regeneration: Where Nanostructure Meets Biology. North Brunswick, NJ: 3DBiotech. 2013. pp. 1–60. doi:10.1142/9789814494847_0001.
  30. ↑ "Treating Parkinson disease with adult stem cells". Journal of Neurological Disorders. 2: 107–109. 2013. doi:10.4172/jnd.100121.
  31. ↑ Young HE, Limnios IJ, Lochner F, McCommon G, Black GF, Coleman JA, Hawkins KC, Black AC Jr (2017). "Cardiovascular disease and adult healing cells: From bench top to bedside". Journal of Stem Cell Research. 1 (3): 1–8. doi:10.33425/2639-9512.1021. 002.
  32. ↑ Young HE, Black GF, Coleman JA, Hawkins KC, Black AC Jr (2017). "Pulmonary diseases and adult healing cells: from bench top to bedside". Journal of Stem Cell Research. 1 (2): 1. doi:10.33425/2639-9512.1013. 003.
  33. ↑ Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. (1999). "Multilineage potential of adult human mesenchymal stem cells". Science. 284 (5411): 143–147. Bibcode:1999Sci...284..143P. doi:10.1126/science.284.5411.143. PMID 10102814.
  34. ↑ Pittenger MF, Discher DE, Péault BM, Phinney DG, Hare JM, Caplan AI (2019). "Mesenchymal stem cell perspective: cell biology to clinical progress". npj Regenerative Medicine. 4 (1) 22. Bibcode:2019npjRM...4...22P. doi:10.1038/s41536-019-0083-6. PMC 6889290. PMID 31815001.
  35. ↑ Hayflick L, Moorhead PS (1961). "The serial cultivation of human diploid cell strains". Experimental Cell Research. 25 (3): 585–621. doi:10.1016/0014-4827(61)90192-6. PMID 13905658.
  36. ↑ Hayflick L (1965). "The limited in vitro lifetime of human diploid cell strains". Experimental Cell Research. 37 (3): 614–636. doi:10.1016/0014-4827(65)90211-9. PMID 14315085.
  37. ↑ Young HE, Henson NL, Black GF, Hawkins KC, Coleman JA, Black AC (2017). "Location and characterization of totipotent stem cells and pluripotent stem cells in the skeletal muscle of the adult rat". Journal of Stem Cell Research. 1 (1): 1–17. doi:10.33425/2639-9512.1002. Article 002.
  38. ↑ Young HE, Speight MO (2021). "Telomerase positive totipotent stem cells in the adult brain. I. Cerebral cortex". Journal of Regenerative Medicine and Biology Research. 2 (1): 1–16. doi:10.46889/jrmbr.2021.2102.
  39. ↑ Young HE, Duplaa C, Romero-Ramos M, Chesselet MF, Vourc'h P, Yost MJ, et al. (2004). "Adult reserve stem cells and their potential for tissue engineering". Cell Biochemistry and Biophysics. 40 (1): 1–80. doi:10.1385/CBB:40:1:1. PMID 14983110.
  40. ↑ Young HE, Duplaa C, Yost MJ, Henson NL, Floyd JA, Detmer K, et al. (2004). "Clonogenic analysis reveals reserve stem cells in postnatal mammals. II. Pluripotent epiblastic-like stem cells". The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology. 277 (1): 178–203. doi:10.1002/ar.a.20000. PMID 14983513.
  41. 1 2 Young HE, Steele TA, Bray RA, Detmer K, Blake LW, Lucas PA, Black AC (1999). "Human pluripotent and progenitor cells display cell surface cluster differentiation markers CD10, CD13, CD56, and MHC class-I". Proceedings of the Society for Experimental Biology and Medicine. 221 (1): 63–71. doi:10.1046/j.1525-1373.1999.d01-55.x. PMID 10320633.
  42. 1 2 Young HE, Speight MO (2020). "Allogeneic and autologous telomerase-positive stem cells as a potential treatment for systemic lupus erythematosus". Stem Cells and Regenerative Medicine. 4 (2): 1–9. doi:10.33425/2639-9512.1054.
  43. 1 2 Young HE, Speight MO (2021). "Alzheimer's disease treated with autologous and allogeneic telomerase-positive stem cells". Stem Cells and Regenerative Medicine. 5 (1): 1–17. doi:10.33425/2639-9512.1058.
  44. 1 2 Young HE, Speight MO (2021). "Treating Parkinson disease with autologous telomerase-positive stem cells, update 2021". Stem Cells and Regenerative Medicine. 5 (1): 1–13. doi:10.33425/2639-9512.1059.
This page is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.