Patents and Publications

Patents:

PLURIPOTENT ADULT STEM CELLS

Patent No.:  US 7,259,011 B2

Date of Patent:  Aug. 21, 2007

Inventors:  Paul Lucas, Sherri Schulz, Sharon P Pine

Summary:

“The invention relates to isolated human pluripotent adult stem cells which express CD13, CD34, CD56 and CD117, and which do not express CD10, which are capable of differentiating in all three germ lineages and differentiated cells derived therefrom.”

This is a composition of matter patent of previous information on the stem cells. It shows regeneration of articular cartilage.

MULTIPOTENT ADULT STEM CELLS :  CHARACTERIZATION AND USE

Pub . No .: US 2019/0338244 A1

Pub . Date : Nov. 7 , 2019

Inventors : Paul LUCAS , Valhalla , NY ( US ) ; Jessica C. Black , Valhalla , NY ( US )

Summary:

“The present invention relates to biomarkers, methods, and composition for characterizing and isolating adult stem cells ( MASCs ) and uses thereof.”

This is the composition of matter patent for the MASCs.  The RNAseq gives a set of gene expression that is unique to MASCs, allowing the determination whether any other cell is an MASC.  It also demonstrates the ability of MASCs to regenerate skin.

Publications:

Note:  We have changed the “name” of the stem cells over time.  Initially, we called them “mesenchymal stem cells”, but then Arnold Caplan and others took the name for cells different than the MASCs.  We have also used the term “pluripotent mesenchymal stem cells” but that is now reserved for embryonic stem cells and induced pluripotent stem cells.  Whatever the name, they are the same cells

Isolation of MASCs from different species and tissues

1. Young, H.E., Sippel, J., Putnam, L.S., Lucas, P.A, and Morrison, D.C.. Enzyme-linked immuno-culture assay (ELICA).  Tiss. Cult. Meth. 14: 31-36, 1992.
2. Young, H.E., Ceballos, E.M., Smith, J.C., Lucas, P.A., and Morrison, D.C. Isolation of embryonic chick myosatellite and pluripotent stem cells.  Tiss. Cult. Meth. 14: 85-92, 1992.
3. Pate, D.W., Southerland, S.S., Grande, D.A., Young, H.E., and Lucas, P.A., Isolation and differentiation of mesenchymal stem cells from rabbit muscle.  Surgical Forum 44: 587-589, 1993.
4. Young, H.E., Ceballos, E.M., Smith, J.C., Mancin, M.L., Wright, R.P., Ragan, B.L., Bushell, I., and Lucas, P.A. Pluripotent mesenchymal stem cells reside within avian connective tissue matrices.  In Vitro Cell. Dev. Biol. 29A: 723-736, 1993.
5. Young, H.E., Mancini, M.L., Wright, R.P., Smith, J.C., Black, A.C. Jr., Reagan, C.R., and Lucas, P.A. Mesenchymal stem cells reside within the connective tissues of many organs.  Dyn. 202: 137-144, 1995.
6. Lucas, P.A., Calcutt, A.F., Southerland, S.S., Wilson, A., Harvey, R. Warejcka, D., and Young, H.E. 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: 449-460, 1995.
7. Warejcka, D., Harvey, R.L, Taylor, B.J.Jr., Young, H.E., and Lucas, P.A. Isolation of a population of mesenchymal stem cells from newborn rat heart. Surg. Res., 62:233-242, 1996.
8. Young HE, Steele TA, Bray RA, Detmer K, Blake LW, Lucas PW, Black AC Jr. Human pluripotent and progenitor cells display cell surface cluster differentiation markers CD10, CD13, CD56, and MHC class-I. Proc Soc Exp Biol Med. 221(1):63-71, 1999.
   Young HE, Steele TA, Bray RA, Hudson J, Floyd JA, Hawkins K, Thomas K, Austin T, Edwards C, Cuzzourt J, Duenzl M, Lucas PA, Black AC Jr. Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec. 2001 Sep 1;264(1):51-62.
9. Russinoff S, Miran S, Gowda, AL, Lucas, PA. Osteosarcoma cells differentiate into phenotypes from all three dermal layers.  Clinical Orthopaedics and Rel. Res., Clin Orthop Relat Res. 2011 Oct;469(10):2895-904.
   
   Differentiation of MASCs in culture (in addition to those papers above)
10. Rogers, J.J., Young, H.E., Adkinson, L.R., Lucas, P.A., and Black, A.C.Jr., Differentiation factors induce expression of muscle, fat, cartilage, and bone in a clone of mouse pluripotent mesenchymal stem cells. Surgeon, 61: 231-236, 1995.
11. Dixon, K., Murphy, R.W., Southerland, S.S., Young, H.E., and Lucas, P.A. Recombinant human bone morphogenetic proteins-2 and 4 (rhBMP-2 and rhBMP-4) induce several mesenchymal phenotypes in culture.  Wound Repair and Regeneration, 4: 374-380, 1996.
12. Young HE, Rogers JJ, Adkison LR, Lucas PA, Black AC. Muscle morphogenetic protein induces myogenic gene expression in swiss-3T3 cells. Wound Repair Regen 6: 543-54, 1998
13. Young HE, Wright RP, Mancini ML, Lucas PA, Reagan CR, Black AC Jr. Bioactive factors affect proliferation and phenotypic expression in progenitor and pluripotent stem cells. Wound Repair Regen. Jan-Feb;6(1):66-75, 1998.
14. Romero-Ramos M, Vourc'h P, Young HE, Lucas PA, Wu Y, Chivatakarn O, Zaman R, Dunkelman N, El-Kalay MA, Chesselet MF. Neuronal differentiation of stem cells isolated from adult muscle. J Neurosci Res. 2002 Sep 15;69(6):894-907.
15. Vourc'h P, Romero-Ramos M, Chivatakarn O, Young HE, Lucas PA, El-Kalay M, Chesselet MF. Isolation and characterization of cells with neurogenic potential from adult skeletal muscle. Biochem Biophys Res Commun. 2004 May 7;317(3):893-901.
16. Vourc'h P, Lacar B, Mignon L, Lucas PA, Young HE, Chesselet MF. Effect of neurturin on multipotent cells isolated from the adult skeletal muscle.  Biochem Biophys Res Commun. 2005 Jun 24;332(1):215-23.
17. Schultz SS, Lucas PA. Human stem cells isolated from adult skeletal muscle differentiate into neural phenotypes. J Neurosci Methods. 2006 Apr 15;152(1-2):144-55.
18. Puzzuoli JC, Hertzeberg M, and Lucas PA. Dexamethasone-Induced Differentiation of Human Multipotent Adult Stem Cells into Phenotypes of All Three Primary Germ Layers in vitro. In preparation
    
    Regeneration with MASCs in animals
19. Grande, D.A., Southerland, S.S., Manji, R., Pate, D.W., Schwartz, R.E., and Lucas, P.A. Repair of articular cartilage defects using mesenchymal stem cells.  Tissue Engineering 1: 345-353, 1995.
20. Lucas, P.A., Warejcka, D.J., Zhang, L-M., Newman, W.H., and Young, H.E. Effect of rat mesenchymal stem cells on development of abdominal adhesions after surgery.  Surg. Res., 62: 229-232 1996.
21. Arriero M, Brodsky SV, Gealekman O, Lucas PA, Goligorsky MS. Adult skeletal muscle stem cells differentiate into endothelial lineage and ameliorate renal dysfunction after acute ischemia. Am J Physiol Renal Physiol. 2004 Oct;287(4):F621-7. Epub 2004 Jun 15.
22. Mignon L, Vourc'h P, Romero-Ramos M, Osztermann P, Young HE, Lucas PA, Chesselet MF. Transplantation of multipotent cells extracted from adult skeletal muscles into the subventricular zone of adult rats.  J Comp Neurol. 2005 Oct 17;491(2):96-108.
23. Schultz SS, Abraham S, Lucas PA. Stem cells isolated from adult rat muscle differentiate across all three dermal lineages.  Wound Repair Regen. 2006 Mar-Apr;14(2):224-31.
24. Lucas PA. Stem cells for mesothelial repair: An understudied modality.  Int J Artif Organs. 2007 Jun;30(6):550-6.
25. Taub, PJ, Jervis, Y, Spangler, M., Mason, JM, and Lucas, PA. Bioengineering of calvaria with adult stem cells.  Plastic Reconstructive Surgery 123(4): 1178-85, 2009. 
26. Achor T, Vigorita V, Sweitlik JF, Marino PD, As;prinio DE, Lucas PA, Repair of Nonunion Defects in Rat Femurs Using Multipotent Adult Stem Cells. Submitted to Tissue Engineering 2023
27. Marino PD, Fasani-Feldberg G, Marshall K, Black J, Lento PA, Arnold A, Lucas PA. Undifferentiated human multipotent adult stem cells (MASCs) survive and differentiate in immunocompetent Sprague-Dawley rats.  Submitted to Tissue Engineering, 2023.
28. Lucas PA, Marino PD, Abraham S, Zhang L. Grose A. Regeneration of Osteochondral Defects Using Multipotent Adult Stem Cells.  In preparation.
29. West A, Marino PD, Talley-Bruns R, and Lucas PA.   Skin Regeneration in adult rats with Multipotent Adult Stem Cells. In preparation.
    
    RNAseq for identification and uniqueness of human MASCs
    
30. Black J, Cumming D, and Lucas PA. Comparative Transcriptome Analysis of Adult MSCs and Multipotent Adult Stem Cells Using RNA-seq. Submitted to Stem Cell, 2019.
31. Black J, Cumming D. and Lucas PA. Comparative Transcriptome Analysis of Human Embryonic Stem Cells and Multipotent Adult Stem Cells Using RNA-seq.  In preparation.
32. Black J, Cumming D. and Lucas PA. Comparative Transcriptome Analysis of Human smooth Muscle Cells and Multipotent Adult Stem Cells Using RNA-seq.  In preparation. 
    
    Human MASC papers (also in list above)
33. Young HE, Steele TA, Bray RA, Detmer K, Blake LW, Lucas PW, Black AC Jr. Human pluripotent and progenitor cells display cell surface cluster differentiation markers CD10, CD13, CD56, and MHC class-I. Proc Soc Exp Biol Med. 221(1):63-71, 1999.
34. Young HE, Steele TA, Bray RA, Hudson J, Floyd JA, Hawkins K, Thomas K, Austin T, Edwards C, Cuzzourt J, Duenzl M, Lucas PA, Black AC Jr. Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec. 2001 Sep 1;264(1):51-62.
35. Schultz SS, Lucas PA. Human stem cells isolated from adult skeletal muscle differentiate into neural phenotypes. J Neurosci Methods. 2006 Apr 15;152(1-2):144-55.
36. Russinoff S, Miran S, Gowda, AL, Lucas, PA. Osteosarcoma cells differentiate into phenotypes from all three dermal layers.  Clinical Orthopaedics and Rel. Res., Clin Orthop Relat Res. 2011 Oct;469(10):2895-904
37. Puzzuoli JC, Hertzeberg M, and Lucas PA. Dexamethasone-Induced Differentiation of Human Multipotent Adult Stem Cells into Phenotypes of All Three Primary Germ Layers in vitro. In preparation
38. Marino PD, Fasani-Feldberg G, Marshall K, Black J, Lento PA, Arnold A, Lucas PA. Undifferentiated human multipotent adult stem cells (MASCs) survive and differentiate in immunocompetent Sprague-Dawley rats.  Submitted to Tissue Engineering, 2023.
39. West A, Marino PD, Talley-Bruns R, and Lucas PA. Skin Regeneration in adult rats with Multipotent Adult Stem Cells. In preparation
40. Black J, Cumming D, and Lucas PA. Comparative Transcriptome Analysis of Adult MSCs and Multipotent Adult Stem Cells Using RNA-seq. Submitted to Stem Cell, 2019.
41. Black J, Cumming D. and Lucas PA. Comparative Transcriptome Analysis of Human Embryonic Stem Cells and Multipotent Adult Stem Cells Using RNA-seq.  In preparation.
42. Black J, Cumming D. and Lucas PA. Comparative Transcriptome Analysis of Human smooth Muscle Cells and Multipotent Adult Stem Cells Using RNA-seq.  In preparation.