Neuron Point-Of-Care Stem Cell Therapy by SCT Vienna
Neuron point-of-care stem cell therapy (N-POCST):
Transplantation of autologous bone marrow-derived stem cells for
traumatic central nervous system disorders, the future of a new
TRAUMATIC BRAIN INJURY
Each year 235 000 persons in US are hospitalized for nonfatal TBI and 50 000 die
(Corrigan et al. 2010)
The prevalence of US civilian residents living with disability following hospitalization
with TBI is 3.2 million (Corrigan et al. 2010).
Despite claims to the contrary, no clear decrease in TBI-related mortality or
improvement of overall outcome has been observed over the past two decades.
(Roozenbeek et al. 2013)
Corrigan, J.D., Selassie, A.W., Orman, J.A.L., 2010. The epidemiology of traumatic brain injury. J. Head Trauma Rehabil. 25, 72–80. doi:10.1097/HTR.0b013e3181ccc8b4.
Roozenbeek, B., Maas, A.I.R., Menon, D.K., 2013. Changing patterns in the epidemiology of traumatic brain injury. Nat. Rev. Neurol. 9, 231–236.
SPINAL CORD INJURY
Every year, between 250 000 and 500 000 people become spinal cord injured. (WHO
“pi al ord i jur is a medically complex
and life-disrupting condition, notes Dr.
Etienne Krug, Director of the Department
of Violence and Injury Prevention and
Disability, WHO. However, spinal cord
injury is preventable, survivable, and need
not preclude good health and social
Is the leading cause of serious long-term disability. (Mozaffarian et al. 2015)
While I speak 5 persons in US will die consequence of stroke. (Mozaffarian et al.
Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association.
Circulation. 2015 ;e29-322.
Current treatment approach
Shin, S.S., Dixon, C.E., Okonkwo, D.O., Richardson, R.M., 2014. Neurostimulation for traumatic brain injury. J. Neurosurg. 121, 1219–1231.
Fehlings, M.G., Vawda, R., 2011. Cellular Treatments for Spinal Cord Injury: The Time is Right for Clinical Trials. Neurotherapeutics 8, 704–
Burns, T.C., Verfaillie, C.M., Low, W.C., 2009. Stem Cells for Ischemic Brain Injury: A Critical Review. J. Comp. Neurol. 515, 125–144.
TBI: Durable treatments for neurological function deficits following TBI have been
elusive, as there are currently no FDA-approved therapeutic modalities for mitigating
the consequences of TBI. (Shin et al. 2014)
SCI: Despite advances in pre-hospital care, medical and surgical management, and
rehabilitation approaches, many SCI sufferers still experience substantial neurological
disability. (Fehlings et al. 2011)
STROKE: Unfortunately, although a plethora of neuroprotective compounds have
shown promise in animal models, no other treatment to date has shown efficacy in
clinical trials (Burns et al. 2009)
Rationale of aBM-SC
A scanning electron microscope picture of a nerve
ending. It has been broken open to reveal vesicles
(orange and blue) containing chemicals used to pass
messages in the nervous system. TINA CARVALHO
Secrete all kind of factors, which
influence the direct environment of
(Gnecchi et al. 2008, Caplan et al.
ASC in BM (HSCs and MSCs)
inflammatory suppression and neural
reconstruction of totally damaged tissues
or preventing partially damaged cells
from evolving to cell demise.
(Erceg and Stojkovic, 2009)
Gnecchi, M., Zhang, Z., Ni, A., Dzau, V.J., 2008. Paracrine mechanisms in adult stem cell signaling and therapy. Circ. Res. 103, 1204–1219.
Caplan, A.I., Dennis, J.E., 2006. Mesenchymal stem cells as trophic mediators. J. Cell. Biochem. 98, 1076–1084. doi:10.1002/jcb.20886
Erceg, S.M.R. and M. Stojkovic, 2009. Human embryonic stem cell differentiation toward regional specific neural precursors. Stem Cells, 1: 78-87. DOI:
Rationale of aBM-SC
Zhang H, Zhang N, Li M, Feng H, Jin W, Zhao H, Chen X, Tian L (2008) Therapeutic angiogenesis of bone marrow mononuclear cells (MNCs) and peripheral blood MNCs:
transplantation for ischemic hindlimb. Ann Vasc Surg 22:238–247
Zeng, R., Wang, L.-W., Hu, Z.-B., Guo, W.-T., Wei, J.-S., Lin, H., Sun, X., Chen, L.-X., Yang, L.-J., 2011. Differentiation of human bone marrow mesenchymal stem cells into
neuron-like cells in vitro. Spine 36, 997–1005. doi:10.1097/BRS.0b013e3181eab76
Bareyre, F.M., 2008. Neuronal repair and replacement in spinal cord injury. J. Neurol. Sci. 265, 63–72. doi:10.1016/j.jns.2007.05.004
Kucia, M., Reca, R., Jala, V.R., Dawn, B., Ratajczak, J., Ratajczak, M.Z., 2005. Bone marrow as a home of heterogenous populations of nonhematopoietic stem cells. Leukemia
19, 1118–1127. doi:10.1038/sj.leu.2403796
aBM-SC are easy to harvest from the iliac crest and a gradient centrifugation can
separate the buffy coat layer, which contains the highest concentration
of HSCs and MSCs.
ASC in BM (HSCs and MSCs)
• Stimulate neovascularization and increase oxygenation (Zhang et al. 2008).
• Transdifferentiate into specific neuronal cells (Zeng et al. 2011).
• Promote synaptic connections (Bareyre et al. 2008).
• Promote neuroplasticity (Kucia et al. 2005).
NO Ethic or immune rejection concrens
Cox CS, Baumgartner JE Jr, Harting MT et al (2011) Autologous bone marrow mononuclear cell therapy for severe traumatic brain injury in children. Neurosurgery 68:588–
Tian, C., Wang, X., Wang, X., Wang, L., Wang, X., Wu, S., Wan, Z., 2013. Autologous bone marrow mesenchymal stem cell therapy in the subacute stage of traumatic brain
injury by lumbar puncture. Exp. Clin. Transplant. Off. J. Middle East Soc. Organ Transplant. 11, 176–181. doi:10.6002/ect.2012.0053
(Cox et al. 2005)
BMN MSC- Open label study in adults with sub acute Subacute sever TBI (N=97) 38 of 97 patients (39.2%)
HSC autolog (1 month) TBI; follow up 15 days. 1 × 106 cells/mL (5 ml.) with TBI improved.
Eleven of 24 patients
(45.8%) with persistent
vegetative state showed
consciousness (P = .024)
(Tian et al. 2013)
Spinal Cord Injury
Park DH, Eve DJ, Chung YG, Sanberg PR (2010) Regenerative medicine for neurological disorders. ScientificWorldJ 10:470–489
Sykova E, Homola A, Mazanec R et al (2006) Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. Cell Transplant 15:675–687
(Park et al. 2005)
(Sykova et al. 2006)
Spinal Cord Injury
Yoon SH, Shim YS, Park YH et al (2007) Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with
granulocyte macrophage-colony stimulating factor: phase I/II clinical trial. Stem Cells 25:2066–2073.
Geffner LF, Santacruz P, Izurieta M et al (2008) Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves
their quality of life: comprehensive case studies. Cell Transplant 17:1277–1293
(Yoon et al. 2007)
(Geffner et al. 2008)
ACUTE VS. CHRONIC ADMINISTRATION
Denes, A., Coutts, G., Lénárt, N., Cruickshank, S.M., Pelegrin, P., Skinner, J., Rothwell, N., Allan, S.M., Brough, D., 2015. AIM2 and NLRC4 inflammasomes contribute with ASC
to acute brain injury independently of NLRP3. Proc. Natl. Acad. Sci. 201419090. doi:10.1073/pnas.1419090112.
Friedrich MA, Martins MP, Araujo MD et al (2012) Intra-arterial infusion of autologous bone-marrow mononuclear cells in patients with moderate to severe middle-
cerebral-artery acute ischemic stroke. Cell Transplant 21(Suppl 1):13–21
Savitz SI, Misra V, Kasam M et al (2011) Intravenous autologous bone marrow mononuclear cells for ischemic stroke. Ann Neurol 70:59–69
These discoveries identify the NLRC4 and AIM2 inflammasomes as potential therapeutic targets for stroke
and provide new insights into how the inflammatory response is regulated after an acute injury to the brain.
(Denes et al. 2015)
(Friedrich et al. 2008)
(Savitz et al. 2008)
ACUTE TREATMENT PROTOCOL
The earl the etter ut if dela ed ot o trai di ated.
POint-of-Care Stem cell Therapy
200 cc of BM
Aktas, M., Radke, T.F., Strauer, B.E., Wernet, P., Kogler, G., 2008. Separation of adult bone marrow mononuclear cells using the automated closed separation
system Sepax. Cytotherapy 10, 203–211. doi:10.1080/14653240701851324.
Cox CS, Baumgartner JE Jr, Harting MT et al (2011) Autologous bone marrow mononuclear cell therapy for severe traumatic brain injury in children.
Autologous bone marrow-derived stem cells transplant with on-site cell concentration
for non-hematopoietic diseases.
The o e arrow olle tio i the a ute phase of the
brain injury did not cause hemodynamic disturbances and
was well tolerated Co et al. TBI i hildre i the
first 8 hours)
Minimal cell manipulation and effective separation
(Aktas et. al. 2008)
After 25 minutes
• IT: 8.5 million CD34+ cells in 12 millilitres.
• IV: 5.6 million CD34+ cells in 8 millilitres.
Matzner, Shaw C., Morrice J., Ruiz-Navarro F., Kobinia G., 2014. CD34+ cell counts and their relationship to clinical factors in 281 patients undergoing
Autologous Stem Cell Transplant, in: World Stem Cell Regenerative Medicine Congress.
Farivar, S., Mohamadzade, Z., Shiari, R., Fahimzad, A., 2015. Neural differentiation of human umbilical cord mesenchymal stem cells by cerebrospinal fluid.
Iran. J. Child Neurol. 9, 87–93.
differentiation of SC
(Matzner et al. 2014)
(Farivar et al. 2015)
CD34+ according to the ISHAGE guidelines.
Viability was assessed with 7-Aminoactinomycin D (7-AAD) dye.
Bakshi, A., Hunter, C., Swanger, S., Lepore, A., Fischer, I., 2004. Minimally invasive delivery of stem cells for spinal cord injury: advantages of the lumbar puncture technique. J. Neurosurg. Spine
1, 330–337. doi:10.3171/spi.2004.1.3.0330
Bakshi, A., Barshinger, A.L., Swanger, S.A., Madhavani, V., Shumsky, J.S., Neuhuber, B., Fischer, I., 2006. Lumbar puncture delivery of bone marrow stromal cells in spinal cord contusion: a novel
method for minimally invasive cell transplantation. J. Neurotrauma 23, 55–65. doi:10.1089/neu.2006.23.55
The use of LP and interventricular
routes allows more efficient
delivery of cells to the injured cord
compared with the intravenous
route. (Bakshi et al. 2004)
We found that MSC delivered by LP
reached the contused spinal cord tissues
and exerted a significant beneficial
effect by reducing cyst and injury size.
(Bakshi et al. 2006)
Our results in chronic patients
61 patients SCI
follow-up after 6 months
Mean time since diagnosis was 72 months
NO PATIENT PRESENT MAYOR SIDE EFFECTS
62% improved the muscular strength
50% improved the spasticity
37% improved the bladder control
93% of them referred a better general health
50% had an improved sensibility