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Abstract

Shanko Y, Navitskaya V, Zamaro A, Krivenko S, Zafranskaya M, Pashkevich S, Koulchitsky S, Takalchik Stukach Y, Denisov A, Kulchitsky V. Prospects of Perineural Administration of Autologous Mesenchymal Stem Cells of Adipose Tissue in Patients with Cerebral Infarction. Biomed J Sci&Tech Res 10(1)-2018. BJSTR. MS.ID.001884. DOI: 10.26717/ BJSTR.2018.10.001884.
Volume 5- Issue 4: 2018
1/3
ISSN: 2574-1241
DOI: 10.26717/BJSTR.2018.10.001884
Kulchitsky Vladimir.
Biomed J Sci & Tech Res
Short Communication
Biomedical Journal of


Introduction
The search for “brain infarction mesenchymal stem cell
therapy” in PubMed on October 01, 2018 showed 233 results.
Experience with MSC therapy in patients with cerebral infarction
is described in 34 articles and search for word combination “brain
infarction mesenchymal stem cell autologous therapy patient”
showed only 9 links. Authors want to pay attention that there are
no results of search for “brain infarction mesenchymal stem cell
autologous perineural therapy patient”. Therefore, there is an empty

Authors recently had only experimental skills in MSC perineural
implantation [1-3]. There are several studies in experimental and
clinical practice when relatively new techniques of SC use are
tested [3,4]. SC are accumulated around damaged brain regions
after their local implantation through trepanation hole to the area
of brain infarct and after systemic injection into bloodstream. Then



Shanko Yuri11234
2522*2
1
2
3
4
5
 : October 08, 2018;  : October 11, 2018
 Kulchitsky Vladimir, Institute of Physiology, National Academy of Sciences, Minsk, Belarus, Europe, Tel:
375172842458; Email:

               
visceral functions is one of the negative consequences of existing therapy. Such state is developed due to persistent structural and functional lack of
central control of various body activities by brain neural networks. Finally, most of the patients have severe invalidities even in distant period after
performed treatment. Therefore, development and implementation of technologies that will allow activating reparative processes in brain after
cerebral infarction is one of prospective tasks.
development and implementation of new technique of cerebral infarctions treatment using autologous mesenchymal stem cells (MSC)
of adipose tissue.
 Authors developed unique technique aimed at formation of conditions for natural migration of stem cells (SC) to the area of cerebral
infarction after their endoscopic administration into nasal submucosa.
 Autologous mesenchymal stem cells (MSC) of 25 patients naturally migrated to the area of cerebral infarction after their administration
into nasal submucosa. The process of MSC differentiation into neuron-like elements after penetration to cranial cavity was previously shown in
               
physiological functions control in 6 months after course therapy with SC assessed by National Institutes of Health Stroke Scale (NIHSS) and Glasgow
Coma Scale (GCS), respectively. Administration of allogeneic SC to patients with cerebral infarctions (n=5) was ineffective.
 Combination of standard therapy of cerebral infarctions with endoscopic perineural implantation of autologous
MSC of adipose tissue is accompanied with activation of reparative processes leading to recovery of neurologic functions.
 Cerebral infarction, Mesenchymal stem cells, Perineural implantation, Patient, Reparative process
GCS: Glasgow Coma Scale; MSC: Mesenchymal Stem Cells; NIHSS: National Institutes of Health Stroke Scale; SC: Stem Cells

 Shanko Y, Navitskaya V, Zamaro A, Krivenko S, Zafranskaya M, Pashkevich S, Koulchitsky S, Takalchik Stukach Y, Denisov
A, Kulchitsky V. Prospects of Perineural Administration of Autologous Mesenchymal Stem Cells of Adipose Tissue in Patients with Cerebral
Infarction. Biomed J Sci&Tech Res 10(1)-2018. BJSTR. MS.ID.001884. DOI: 10.26717/ BJSTR.2018.10.001884.
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Volume 10- Issue 1: 2018
SC differentiate into neuron-like elements [5]. It is obvious that
technique of MSC perineural implantation into peripheral areas of
cranial nerve endings (e.g. nasal cavity) [1-3] positively differs from
other cellular technologies such as intracerebral MSC implantation
 
[5-7].
Materials and Methods
Technique of perineural delivery of MSC into brain after their
endoscopic administration into nasal submucosa was developed
and implemented [1,3]. The method was used in addition to standard
therapy of acute cerebral infarction. 25 patients were examined. 12

group, 8 patients with secondary brain infarctions after intracranial
hemorrhages - into second group (aged 27-73 years, 40.25 mean).
        
perineural administration of MSC using the previously described
technique [3]. Patients with primary cerebral infarctions from
the third group (n=5) received standard therapy with allogeneic
MSC. 50ml of adipose tissue was taken from umbilical area of each
         
using previously described technique [3] and then endoscopic
threefold intranasal implantation of autologous MSC in the amount
of 5-12×106 cells was performed with the intervals of 5-9 days.
Allogeneic SC were prepared from donor material in the absence
of conditions for autologous tissues retrieval and administered
perineurally to patients from the third group.
Results
Use of allogeneic MSC by means of their perineural delivery to
 

         
improved after combination of classic therapy of cerebral
infarctions with intranasal implantation of autologous MSC. This
outcome is a valid argument in discussion on reasonability of
autologous and allogeneic biomaterial use. Obtained data allow
recommending autologous MSC as basic cellular technology for
         
          
(within 1 point of British medical research council scale) recovery
of certain neurologic functions in 24 hours after each implantation
of autologous MSC (Figure 1).
Figure 1: Efcacy assessment of cell therapy of primary cerebral infarctions (n=12) was performed in the early period after implantation and
in 6 months. Injections were made on Day 1 (rst), Day 7 (second) and Day 13 (third).
In particular, NIHSS score changed in patients with primary
cerebral infarctions (n=12) from 14.2 at the beginning to 1.8 in 6
months; none of them had recurrent cerebral infarctions during
one year of observation. In comparison, NIHSS score changed
in patients of control group (n=20, classic therapy of cerebral
infarctions) from 14.4 at the beginning to 9.8 in 6 months; three of
them (15%) had recurrent cerebral infarctions during six months
of observation.

multiple secondary cerebral infarctions (n=8) because all of them
were in comatose state and NIHSS assessment was not applicable.
Combined therapy (classic standard of care and administration of
autologous MSC) was started at 6.2 GCS. Second group of patients
did not show rapid regress of neurologic disorders, even after
each SC implantation. These patients had GCS score 9.2 after the
end of therapy with SC and NIHSS score 12.3 in six months after
perineural implantation of MSC and standard therapy together with
rehabilitation. It was hard to compare with control group, because
one patient died there, three were in vegetative state and the last
one had GCS score 28.0. However, it is important that there were no
complications in any case.
Discussion and Conclusion
Combination of classic therapy of cerebral infarctions with
endoscopic intranasal perineural implantation of autologous MSC,
which migrate to the area of brain infarct, is accompanied with
formation of conditions for activation of reparative processes
leading to recovery of neurologic functions [3,8].
Positive results of clinical observations also led to appearance
of several conclusions and questions. No clear dependence was
established between effectiveness of reparative processes and
amount of implanted SC [8,9]. Diversity of effects determined by
 Volume 10- Issue 1: 2018
 Shanko Y, Navitskaya V, Zamaro A, Krivenko S, Zafranskaya M, Pashkevich S, Koulchitsky S, Takalchik Stukach Y, Denisov
A, Kulchitsky V. Prospects of Perineural Administration of Autologous Mesenchymal Stem Cells of Adipose Tissue in Patients with Cerebral
Infarction. Biomed J Sci&Tech Res 10(1)-2018. BJSTR. MS.ID.001884. DOI: 10.26717/ BJSTR.2018.10.001884.
3/3
individual features of patients and variety of clinical performance
of cerebral infarction was revealed. No dependence between
reparative effect and the period of cellular therapy beginning was
established. Relatively short period of observation (about one
         
of long-term effect of cellular therapy (e.g. in one-two years) after
cerebral infarction development and beginning of therapy. There
are also some questions remained unclear according effectiveness
of additional implantations of autologous MSC of adipose tissue in
distant periods after treatment beginning (after one or more years).
The mechanism of neurotrophic effects after autologous MSC use
and recovery of neural network functions in brain was supposed,
but not proved [3,10,11]. Therefore, the future task aimed at
analysis of activation of neurotrophic and other endogenous
      
[1,3,12,13].
Acknowledgement
This pooled analysis was funded by SSTP “New methods of
medical care”, section “Transplantation of cells, tissues and organs”
(2016-2020), and by grant OOO “Synergy”.
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ISSN: 2574-1241
DOI: 10.26717/BJSTR.2018.10.001884
Kulchitsky Vladimir. Biomed J Sci & Tech Res
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