Safety Study of Intravenously Administered Human Cord Blood Stem Cells in the Treatment of Symptoms Related to Chronic Inflammation
Numerous investigations suggest that Mesenchymal
Stem Cells (MSCs) in general represent a valuable tool for therapy of
symptoms related to chronic inflammatory diseases. Blue Horizon
Stem Cell Therapy Program is a leading provider of adult and
children’s stem cell therapies. Uniquely we have safely and
efficiently treated more than 600 patients with documenting each
procedure. The purpose of our study is primarily to monitor the
immune response in order to validate the safety of intravenous
infusion of human umbilical cord blood derived MSCs (UC-MSCs),
and secondly, to evaluate effects on biomarkers associated with
chronic inflammation. Nine patients were treated for conditions
associated with chronic inflammation and for the purpose of antiaging.
They have been given one intravenous infusion of UCMSCs.
Our study of blood test markers of 9 patients with chronic
inflammation before and within three months after MSCs treatment
demonstrates that there is no significant changes and MSCs treatment
was safe for the patients. Analysis of different indicators of chronic
inflammation and aging included in initial, 24-hours, two weeks and
three months protocols showed that stem cell treatment was safe for
the patients; there were no adverse reactions. Moreover data from
follow up protocols demonstrates significant improvement in energy
level, hair, nails growth and skin conditions. Intravenously
administered UC-MSCs were safe and effective in the improvement
of symptoms related to chronic inflammation. Further close
monitoring and inclusion of more patients are necessary to fully
characterize the advantages of UC-MSCs application in treatment of
symptoms related to chronic inflammation.
[1] N. Khansari, Y. Shakiba, M. Mahmoudi. Chronic inflammation and
oxidative stress as a major cause of age-related diseases and cancer.
Recent Pat Inflamm Allergy Drug Discov 2009;3(1):73-80.
[2] P. C. Calder, R. Albers, J. M. Antoine, S. Blum et al. Inflammatory
disease processes and interactions with nutrition. Br J Nutr 2009;101
Suppl 1:S1-45.
[3] J. R. Lukens, J. M. Gross, T. D. Kanneganti. IL-1 family cytokines
trigger sterile inflammatory disease. Front Immunol 2012; 3: 315
[4] J. Voswinkel, S. Francois, J. M. Simon, M. Benderitter, N. C. Gorin, M.
Mohty, L. Fouillard, A. Chapel. Use of mesenchymal stem cells (MSC)
in chronic inflammatory fistulizing and fibrotic diseases: a
comprehensive review. Clin Rev Allergy Immunol 2013;45(2):180-92.
[5] C. Perdikogianni, H. Dimitriou, E. Stiakaki, G. Martimianaki, M.
Kalmanti. Could cord blood be a source of mesenchymal stromal cells
for clinical use? Cytotherapy 2008; 10(5):452-9.
[6] A. Erices, P. Conget, J. J. Minguell. Mesenchymal progenitor cells in
human umbilical cord blood. Br J Haematol 2000;109(1):235–242.
[7] P. S. In 't Anker, S. A. Scherjon, C. Kleijburg-van der Keur, G. M. de
Groot-Swings, F. H. Claas, W. E. Fibbe et al. Isolation of mesenchymal
stem cells of fetal or maternal origin from human placenta. Stem Cells
2004; 22(7):1338–1345.3.
[8] R. A. Panepucci, J. L. Siufi, W. A. Silva Jr, R. Proto-Siquiera, Neder L,
Orellana M, et al. Comparison of gene expression of umbilical cord vein
and bone marrow-derived mesenchymal stem cells. Stem Cells 2004;
22(7):1263–1278.
[9] Y. Jiang, B. N. Jahagirdar, R. L. Reinhardt et al. Pluripotency of
mesenchymal stem cells derived from adult marrow. Nature 2002;
418(6893):41-9.
[10] K. Mareschi, I. Ferrero, D. Rustichelli, S. Aschero, L. Gammaitoni, M.
Aglietta, E. Madon, F. Fagioli. Expansion of mesenchymal stem cells
isolated from pediatric and adult donor bone marrow. J Cell Biochem
2006; 97(4):744-54.
[11] C. Campagnoli, I. A. Roberts, S. Kumar, P. R. Bennett, I. Bellantuono,
N. M. Fisk. Identification of mesenchymal stem/progenitor cells in
human first-trimester fetal blood, liver, and bonemarrow. Blood
2001;98(8):2396–2402.
[12] H. S. Wang, S. C. Hung, S. T. Peng, C. C. Huang, H. M. Wei, Y. J. Guo
et al. Mesenchymal stem cells in the Wharton’s jelly of the human
umbilical cord. Stem Cells 2004;22(7):1330–1337.
[13] L. F. Wu, N. N. Wang, Y. S. Liu, X. Wei. Differentiation of Wharton's
jelly primitive stromal cells into insulin-producing cells in comparison
with bone marrow mesenchymal stem cells. Tissue Eng Part A 2009;
15(10):2865-73.
[14] R. Sarugaser, D. Lickorish, D. Baksh, M. M. Hosseini, Davies JE.
Human umbilical cord perivascular (HUCPV) cells: a source of
mesenchymal progenitors. Stem Cells 2005;23(2):220–229.
[15] L. L. Lu, Y. J. Liu, S. G. Yang, Q. J. Zhao, X. Wang, W. Gong, et al.
Isolation and characterization of human umbilical cord mesenchymal
stem cells with hematopoiesis- supportive function and other potentials.
Haematologica 2006;91(8):1017–1026.
[16] A. Can, S. Karahuseyinoglu. Concise review: human umbilical cord
stroma with regard to the source of fetus-derived stem cells. Stem Cells
2007;25(11):2886–2895.
[17] K. H. Wu, B. Zhou, S. H. Lu, B. Feng, S. G. Yang, W. T. Du et al. In
vitro and in vivo differentiation of human umbilical cord derived stem
cells into endothelial cells. J Cell Biochem 2007;100(3):608–616.
[18] P. C. Jiang, W. P. Xiong, G. Wang, C. Ma, W. Q. Yao, S. F. Kendell, B.
M. Mehling, X. H. Yuan, D. C. Wu. A clinical trial report of autologous
bone marrow-derived mesenchymal stem cell transplantation in patients
with spinal cord injury. Exp Ther Med 2013;6(1):140-146.
[19] O. Ringdén, M. Uzunel, B. Sundberg, L. Lönnies, S. Nava, J.
Gustafsson, L. Henningsohn, K. Le Blanc. Tissue repair using allogeneic
mesenchymal stem cells for hemorrhagic cystitis, pneumomediastinum
and perforated colon. Leukemia 2007;21(11):2271-6.
[20] D. García-Olmo, M. García-Arranz, D. Herreros, I. Pascual, Peiro C,
Rodríguez-Montes JA. A phase I clinical trial of the treatment of Crohn's
fistula by adipose mesenchymal stem cell transplantation. Dis Colon
Rectum 2005;48(7):1416-23.
[21] K. S. Kang, S. W. Kim, Y. H. Oh, J. W. Yu, K. Y. Kim, H. K. Park, C.
H. Song, H. Han. A 37-year-old spinal cord-injured female patient,
transplanted of multipotent stem cells from human UC blood, with
improved sensory perception and mobility, both functionally and
morphologically: a case study. Cytotherapy 2005;7(4):368-73.
[22] L. Mazzini, K. Mareschi, I. Ferrero, E. Vassallo, G. Oliveri, R.
Boccaletti, L. Testa, S. Livigni, F. Fagioli. Autologous mesenchymal
stem cells: clinical applications in amyotrophic lateral sclerosis. Neurol
Res 2006;28(5):523-6.
[23] A. V. Bystrov, Y. A. Polyaev, M. A. Pogodina, M. F. Rasulov, M. E.
Krasheninnikov, N. A. Onishchenko. Use of autologous bone marrow
mesenchymal stem cells for healing of free full-thickness skin graft in a
zone with pronounced hypoperfusion of soft tissues caused by
arteriovenous shunting. Bull Exp Biol Med 2006;142(1):123-8.
[24] V. Falanga, S. Iwamoto, M. Chartier, T. Yufit, J. Butmarc, N. Kouttab,
D. Shrayer, P. Carson. Autologous bone marrow-derived cultured
mesenchymal stem cells delivered in a fibrin spray accelerate healing in
murine and human cutaneous wounds. Tissue Eng 2007;13(6):1299-312.
[25] G. E. Kilroy, S. J. Foster, X. Wu, J. Ruiz, S. Sherwood, A. Heifetz, J. W.
Ludlow, D. M. Stricker, S. Potiny, P. Green, Y. D. Halvorsen, B.
Cheatham, R. W. Storms, J. M. Gimble. Cytokine profile of human
adipose-derived stem cells: expression of angiogenic, hematopoietic, and
pro-inflammatory factors. J Cell Physiol 2007; 212(3):702-9.
[26] E. Meliga, B. M. Strem, H. J. Duckers, P. W. Serruys. Adipose-derived
cells. Cell Transplant 2007; 16(9):963-70.
[27] W. S. Kim, B. S. Park, S. H. Park, H. K. Kim, J. H. Sung. Antiwrinkle
effect of adipose-derived stem cell: activation of dermal fibroblast by
secretory factors. J Dermatol Sci 2009; 53(2):96-102.
[28] H. Nakagawa, S. Akita, M. Fukui, T. Fujii, K. Akino. Human
mesenchymal stem cells successfully improve skin-substitute wound
healing. Br J Dermatol 2005;153(1):29-36.
[29] S. Zhang, Z. Dong, Z. Peng, F. Lu. Anti-aging effect of adipose-derived
stem cells in a mouse model of skin aging induced by D-galactose. PLoS
One 2014;9(5):e97573.
[30] K. Al-Refu. Stem cells and alopecia: a review of pathogenesis. Br J
Dermatol 2012;167(3):479-84. emonstrated
[31] H. Fukuoka, H. Suga, K. Narita, R. Watanabe, S. Shintani. The Latest
Advance in Hair Regeneration Therapy Using Proteins Secreted by
Adipose-Derived Stem Cells. The American Journal of Cosmetic
Surgery 2012; 29:4.
[1] N. Khansari, Y. Shakiba, M. Mahmoudi. Chronic inflammation and
oxidative stress as a major cause of age-related diseases and cancer.
Recent Pat Inflamm Allergy Drug Discov 2009;3(1):73-80.
[2] P. C. Calder, R. Albers, J. M. Antoine, S. Blum et al. Inflammatory
disease processes and interactions with nutrition. Br J Nutr 2009;101
Suppl 1:S1-45.
[3] J. R. Lukens, J. M. Gross, T. D. Kanneganti. IL-1 family cytokines
trigger sterile inflammatory disease. Front Immunol 2012; 3: 315
[4] J. Voswinkel, S. Francois, J. M. Simon, M. Benderitter, N. C. Gorin, M.
Mohty, L. Fouillard, A. Chapel. Use of mesenchymal stem cells (MSC)
in chronic inflammatory fistulizing and fibrotic diseases: a
comprehensive review. Clin Rev Allergy Immunol 2013;45(2):180-92.
[5] C. Perdikogianni, H. Dimitriou, E. Stiakaki, G. Martimianaki, M.
Kalmanti. Could cord blood be a source of mesenchymal stromal cells
for clinical use? Cytotherapy 2008; 10(5):452-9.
[6] A. Erices, P. Conget, J. J. Minguell. Mesenchymal progenitor cells in
human umbilical cord blood. Br J Haematol 2000;109(1):235–242.
[7] P. S. In 't Anker, S. A. Scherjon, C. Kleijburg-van der Keur, G. M. de
Groot-Swings, F. H. Claas, W. E. Fibbe et al. Isolation of mesenchymal
stem cells of fetal or maternal origin from human placenta. Stem Cells
2004; 22(7):1338–1345.3.
[8] R. A. Panepucci, J. L. Siufi, W. A. Silva Jr, R. Proto-Siquiera, Neder L,
Orellana M, et al. Comparison of gene expression of umbilical cord vein
and bone marrow-derived mesenchymal stem cells. Stem Cells 2004;
22(7):1263–1278.
[9] Y. Jiang, B. N. Jahagirdar, R. L. Reinhardt et al. Pluripotency of
mesenchymal stem cells derived from adult marrow. Nature 2002;
418(6893):41-9.
[10] K. Mareschi, I. Ferrero, D. Rustichelli, S. Aschero, L. Gammaitoni, M.
Aglietta, E. Madon, F. Fagioli. Expansion of mesenchymal stem cells
isolated from pediatric and adult donor bone marrow. J Cell Biochem
2006; 97(4):744-54.
[11] C. Campagnoli, I. A. Roberts, S. Kumar, P. R. Bennett, I. Bellantuono,
N. M. Fisk. Identification of mesenchymal stem/progenitor cells in
human first-trimester fetal blood, liver, and bonemarrow. Blood
2001;98(8):2396–2402.
[12] H. S. Wang, S. C. Hung, S. T. Peng, C. C. Huang, H. M. Wei, Y. J. Guo
et al. Mesenchymal stem cells in the Wharton’s jelly of the human
umbilical cord. Stem Cells 2004;22(7):1330–1337.
[13] L. F. Wu, N. N. Wang, Y. S. Liu, X. Wei. Differentiation of Wharton's
jelly primitive stromal cells into insulin-producing cells in comparison
with bone marrow mesenchymal stem cells. Tissue Eng Part A 2009;
15(10):2865-73.
[14] R. Sarugaser, D. Lickorish, D. Baksh, M. M. Hosseini, Davies JE.
Human umbilical cord perivascular (HUCPV) cells: a source of
mesenchymal progenitors. Stem Cells 2005;23(2):220–229.
[15] L. L. Lu, Y. J. Liu, S. G. Yang, Q. J. Zhao, X. Wang, W. Gong, et al.
Isolation and characterization of human umbilical cord mesenchymal
stem cells with hematopoiesis- supportive function and other potentials.
Haematologica 2006;91(8):1017–1026.
[16] A. Can, S. Karahuseyinoglu. Concise review: human umbilical cord
stroma with regard to the source of fetus-derived stem cells. Stem Cells
2007;25(11):2886–2895.
[17] K. H. Wu, B. Zhou, S. H. Lu, B. Feng, S. G. Yang, W. T. Du et al. In
vitro and in vivo differentiation of human umbilical cord derived stem
cells into endothelial cells. J Cell Biochem 2007;100(3):608–616.
[18] P. C. Jiang, W. P. Xiong, G. Wang, C. Ma, W. Q. Yao, S. F. Kendell, B.
M. Mehling, X. H. Yuan, D. C. Wu. A clinical trial report of autologous
bone marrow-derived mesenchymal stem cell transplantation in patients
with spinal cord injury. Exp Ther Med 2013;6(1):140-146.
[19] O. Ringdén, M. Uzunel, B. Sundberg, L. Lönnies, S. Nava, J.
Gustafsson, L. Henningsohn, K. Le Blanc. Tissue repair using allogeneic
mesenchymal stem cells for hemorrhagic cystitis, pneumomediastinum
and perforated colon. Leukemia 2007;21(11):2271-6.
[20] D. García-Olmo, M. García-Arranz, D. Herreros, I. Pascual, Peiro C,
Rodríguez-Montes JA. A phase I clinical trial of the treatment of Crohn's
fistula by adipose mesenchymal stem cell transplantation. Dis Colon
Rectum 2005;48(7):1416-23.
[21] K. S. Kang, S. W. Kim, Y. H. Oh, J. W. Yu, K. Y. Kim, H. K. Park, C.
H. Song, H. Han. A 37-year-old spinal cord-injured female patient,
transplanted of multipotent stem cells from human UC blood, with
improved sensory perception and mobility, both functionally and
morphologically: a case study. Cytotherapy 2005;7(4):368-73.
[22] L. Mazzini, K. Mareschi, I. Ferrero, E. Vassallo, G. Oliveri, R.
Boccaletti, L. Testa, S. Livigni, F. Fagioli. Autologous mesenchymal
stem cells: clinical applications in amyotrophic lateral sclerosis. Neurol
Res 2006;28(5):523-6.
[23] A. V. Bystrov, Y. A. Polyaev, M. A. Pogodina, M. F. Rasulov, M. E.
Krasheninnikov, N. A. Onishchenko. Use of autologous bone marrow
mesenchymal stem cells for healing of free full-thickness skin graft in a
zone with pronounced hypoperfusion of soft tissues caused by
arteriovenous shunting. Bull Exp Biol Med 2006;142(1):123-8.
[24] V. Falanga, S. Iwamoto, M. Chartier, T. Yufit, J. Butmarc, N. Kouttab,
D. Shrayer, P. Carson. Autologous bone marrow-derived cultured
mesenchymal stem cells delivered in a fibrin spray accelerate healing in
murine and human cutaneous wounds. Tissue Eng 2007;13(6):1299-312.
[25] G. E. Kilroy, S. J. Foster, X. Wu, J. Ruiz, S. Sherwood, A. Heifetz, J. W.
Ludlow, D. M. Stricker, S. Potiny, P. Green, Y. D. Halvorsen, B.
Cheatham, R. W. Storms, J. M. Gimble. Cytokine profile of human
adipose-derived stem cells: expression of angiogenic, hematopoietic, and
pro-inflammatory factors. J Cell Physiol 2007; 212(3):702-9.
[26] E. Meliga, B. M. Strem, H. J. Duckers, P. W. Serruys. Adipose-derived
cells. Cell Transplant 2007; 16(9):963-70.
[27] W. S. Kim, B. S. Park, S. H. Park, H. K. Kim, J. H. Sung. Antiwrinkle
effect of adipose-derived stem cell: activation of dermal fibroblast by
secretory factors. J Dermatol Sci 2009; 53(2):96-102.
[28] H. Nakagawa, S. Akita, M. Fukui, T. Fujii, K. Akino. Human
mesenchymal stem cells successfully improve skin-substitute wound
healing. Br J Dermatol 2005;153(1):29-36.
[29] S. Zhang, Z. Dong, Z. Peng, F. Lu. Anti-aging effect of adipose-derived
stem cells in a mouse model of skin aging induced by D-galactose. PLoS
One 2014;9(5):e97573.
[30] K. Al-Refu. Stem cells and alopecia: a review of pathogenesis. Br J
Dermatol 2012;167(3):479-84. emonstrated
[31] H. Fukuoka, H. Suga, K. Narita, R. Watanabe, S. Shintani. The Latest
Advance in Hair Regeneration Therapy Using Proteins Secreted by
Adipose-Derived Stem Cells. The American Journal of Cosmetic
Surgery 2012; 29:4.
@article{"International Journal of Medical, Medicine and Health Sciences:70840", author = "Brian M. Mehling and Louis Quartararo and Marine Manvelyan and Paul Wang and Dong-Cheng Wu", title = "Safety Study of Intravenously Administered Human Cord Blood Stem Cells in the Treatment of Symptoms Related to Chronic Inflammation", abstract = "Numerous investigations suggest that Mesenchymal
Stem Cells (MSCs) in general represent a valuable tool for therapy of
symptoms related to chronic inflammatory diseases. Blue Horizon
Stem Cell Therapy Program is a leading provider of adult and
children’s stem cell therapies. Uniquely we have safely and
efficiently treated more than 600 patients with documenting each
procedure. The purpose of our study is primarily to monitor the
immune response in order to validate the safety of intravenous
infusion of human umbilical cord blood derived MSCs (UC-MSCs),
and secondly, to evaluate effects on biomarkers associated with
chronic inflammation. Nine patients were treated for conditions
associated with chronic inflammation and for the purpose of antiaging.
They have been given one intravenous infusion of UCMSCs.
Our study of blood test markers of 9 patients with chronic
inflammation before and within three months after MSCs treatment
demonstrates that there is no significant changes and MSCs treatment
was safe for the patients. Analysis of different indicators of chronic
inflammation and aging included in initial, 24-hours, two weeks and
three months protocols showed that stem cell treatment was safe for
the patients; there were no adverse reactions. Moreover data from
follow up protocols demonstrates significant improvement in energy
level, hair, nails growth and skin conditions. Intravenously
administered UC-MSCs were safe and effective in the improvement
of symptoms related to chronic inflammation. Further close
monitoring and inclusion of more patients are necessary to fully
characterize the advantages of UC-MSCs application in treatment of
symptoms related to chronic inflammation.", keywords = "Chronic inflammatory diseases, intravenous
infusion, mesenchymal stem cells (MSCs), umbilical cord blood.", volume = "9", number = "7", pages = "573-4", }
