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\begin{document}

\title{A Case Report: The First Show Phenomenon In The Treatment Of Spinal Cord
Injury With Regentime Procedure Using Autologous Bone Marrow-Derived
Stem Cells}



\author[1]{Rita Boulos}%
\author[1]{lea nemer}%
\author[1]{Vanessa Mansour}%
\author[1]{Cynthia Najjoum}%
\author[1]{Elsa Asmar}%
\author[1]{Nassim Abi Chahine}%
\affil[1]{ACE Cells Lab Limited}%


\vspace{-1em}



  
  \date{May 21, 2024}


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\textbf{A Case Report: The First Show Phenomenon In The Treatment Of
Spinal Cord Injury With Regentime Procedure Using Autologous Bone
Marrow-Derived Stem Cells}

Rita T. Boulos \textsuperscript{a+}, Lea I. Nemer\textsuperscript{b+},
Vanessa J. Mansour \textsuperscript{c+}, Cynthia F.
Najjoum\textsuperscript{d++},

Elsa A. Asmar \textsuperscript{e++} and Nassim H. Abi
Chahine\textsuperscript{f*}

\textsuperscript{+} Authors' equal contribution

\textsuperscript{++} Authors' equal contribution

\begin{enumerate}
\tightlist
\item
  Stem Cell Transplantation/Neurology, ACE Cells Lab Limited, Beirut, LB
\item
  Stem Cell Transplantation/Molecular Biology, ACE Cells Lab Limited,
  Beirut, LB
\item
  Stem Cell Transplantation/Infectious Diseases/Immunology, ACE Cells
  Lab Limited, Beirut, LB
\item
  Stem Cell Transplantation/Infectious Diseases/Immunology, ACE Cells
  Lab Limited, Beirut, LB
\item
  Stem Cell Transplantation/Functional Genomics/Proteomics, ACE Cells
  Lab Limited, Beirut, LB
\item
  Stem Cell Transplantation/Neurological Surgery, ACE Cells Lab Limited,
  Beirut, LB
\end{enumerate}

* Correspondence to:

Dr. Nassim H. Abi Chahine

Tel: +9613082498

E-mail: info@regentime.com

\textbf{Acknowledgments}

Not applicable. No funding declared.

\textbf{Conflict of interest statement}

Intellectual Property Office Priority Document Access Service (PDAS)
Reference: Regentime Brain Patent application number: GB1712971.9 Full
name of the first applicant: Abi Chahin, Dr. Nassim Date 13 August 2017

\textbf{Key Clinical message}

Our therapy for SCI patients demonstrated the 'first show phenomenon',
with our patient experiencing significant symptom improvement within the
first few days of treatment. This suggests that our therapy may have the
potential to provide rapid and meaningful clinical benefits for SCI
patients.

\textbf{ABSTRACT}

This case report demonstrates `the first show phenomenon' following
Regentime stem cell therapy applied to a spinal cord injury patient. A
40-year-old gentleman sustained a ballistic injury at the level of T9,
resulting in complete bilateral motor and sensory loss from T9 and
below. He was treated with autologous bone marrow-derived mononuclear
stem cells injected into his spinal canal 2.5 years after his injury.
Follow-up during the first-week post-transplantation showed early
symptom improvement termed ``the first show post phenomenon''. He
regained sensation to light touch in his lower limbs by the end of week
1 and reported no serious implications or complications.

\emph{\textbf{Keywords:} Spinal cord injury, Regentime therapy, Stem
cell therapy, First show phenomenon, autologous bone marrow-derived
mononuclear stem cells.}

\textbf{INTRODUCTION:}

Spinal cord injury (SCI) is a critical health condition that can result
in substantial morbidity and long-term disability. The disruption of the
electrical influx running through the spinal cord leads to sensory-motor
loss of function below the injury level {[}1{]}. The leading causes of
SCI include motor vehicle accidents, violence (especially gunshot
wounds), sports accidents, and falls among others {[}2{]}. The
pathophysiology of SCI consists of primary and secondary phases of
injury. The primary phase relates to the early stage immediately after
the injury and includes neural parenchyma destruction, axonal network
disruption, glial membrane disruption, and hemorrhage. The secondary
phase follows and is manifested by early vascular damage, free radical
formation, inflammation, necrosis, neuronal apoptosis, Wallerian
degeneration, axonal demyelination and remodeling, and late glial scar
formation and maturation {[}3{]}.

Despite significant advances in new therapeutic and rehabilitation
approaches, there is no treatment for SCI yet. However, several clinical
trials were conducted to assess the long-term therapeutic efficacy of
bone marrow-derived stem cell transplantation on SCI patients and found
promising results {[}4, 5{]}. We report the case of a 40-year-old
gentleman with a past medical history of SCI at the level of T9 two and
a half years ago, with an American Spinal Injury Association (ASIA)
impairment scale grade A, who underwent the Regentime procedure
{[}6{]}. The patient gained lower limb sensation and improved to ASIA
impairment scale grade B as early as one-week post stem cell
transplantation, a manifestation that we call `the first show
phenomenon'. The major focus of this case report is the role of
Regentime therapy in optimizing neuro-regeneration by administering
autologous Bone Marrow-Derived Mononuclear Cells (BM-MNCs).

\textbf{CASE PRESENTATION}

A 40-year-old man was presented to our hospital outpatient clinic for a
SCI stem cell treatment trial. He had a 2.5 year history of a ballistic
injury that resulted in a spinal cord thoracic lesion at the level of
T9, for which he underwent posterior decompression and fusion after 24
hours (Figure 1). The patient presented with paralysis, loss of
sensation in the lower extremities, and loss of\selectlanguage{english}
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\textbf{Figure 1} : the thoracic injury at the level of T9.

bladder and bowel control since the injury. On physical examination, he
had a bilateral loss of sensation (pain, temperature, touch, vibration,
and proprioception) below the level of injury and a motor power of 0/5
in his lower limbs.

The patient decided to attempt the Regentime Procedure. Before therapy,
written consent was obtained from the patient, and a day-by-day
follow-up was done during the first weeks. A periodic 1-month follow-up
was scheduled for later assessment of safety and improvement.

\textbf{The Regentime Procedure} {[}6{]}:

Pre-lab stage

During the first 2 days, the patient was injected with a total of 4
doses of 300 mcg of Granulocyte Colony Stimulating Factor
intramuscularly separated by 12 hours each. Eight hours after the last
dose, an increase in the white blood cell count was registered 28 000
cells/mL.

The bone marrow collection stage

Bone marrow aspiration was done, in which 100 mL were collected from
each posterior superior iliac crest, using 4 aspiration syringes filled
with 25,000 units of 10\% heparin sodium each. The aspirate was
transferred to a transfusion bag after the removal of sodium citrate
under sterile conditions. The bag was held at 22\selectlanguage{ngerman}ºC on a slow
three-dimensional laboratory shaker.

Laboratory stage

The cellular buffy coat containing stem cells was collected after
centrifugation.

Transplantation stage

After 24 hours of incubation, the patient received progenitor stem cells
via direct injection in the operating room after the hardware removal.
Following the surgery, the patient also had an intravenous
administration of around 100 million stem cells (1 mL) in 100 mL of
normal saline solution.

Post-transplantation stage

The patient stayed in his hospital room for several days to monitor
vital signs and record any undesirable effects.

\textbf{Results}

Postoperatively, the patient was recovering smoothly with no significant
complaints. He started to regain sensation in his right lower limb upon
touch on day 1 after stem cell transplantation. Towards the end of the
first-week, he was able to detect touch in both of his lower limbs.
However, two to three weeks after transplantation, the early
improvements declined. Moreover, he could not distinguish between two
points applied simultaneously to his legs bilaterally, did not feel
changes of temperature applied on his lower limbs, and maintained an
absent joint position sense bilaterally.

\textbf{DISCUSSION}

Every year, around 1 million persons suffer from SCI, causing
significant morbidity and permanent motor, sensory, and autonomic
dysfunction {[}\selectlanguage{english}1, \selectlanguage{english}3, and \selectlanguage{english}7{]}. Stem cell therapy for SCI success rate
depends on when the injury first occurred and on its grade due to the
heterogeneity of SCI pathophysiology. Our patient sustained a SCI that
resulted in a total bilateral loss of sensory and motor function below
the injury level. He underwent the Regentime procedure via both direct
injection in the operating room and intravenous routes 2.5 years after
injury. Regentime therapy first show phenomenon was evident during the
first days post-transplantation when the patient regained sensation to
touch in his lower limbs. However, this phenomenon has shown to be
transient few weeks post-transplantation. Noting that he did not
complain of any undesirable effects during this follow-up period. Our
results suggest that the Regentime procedure seems to be safe and
effective for patients suffering from SCI.

The first cells utilized for treating SCI in both experimental and
clinical trials were Bone Marrow-Derived Mesenchymal Stem Cells
(BM-MSCs) {[}\selectlanguage{english}8{]}. Motor, sensory, and autonomic functions were
partially improved in primary studies involving thoracic spinal cord
contusion and BM-MSCs transplantation {[}\selectlanguage{english}5{]}. Similar improvements
were recorded in other studies whether BM-MSCs were given via direct
injection into the spinal canal during a surgical act {[}\selectlanguage{english}9{]},
intrathecally {[}\selectlanguage{english}10{]}, or intravenously {[}\selectlanguage{english}11{]}. Also, stem cell
treatment was shown to result in improvement in the ASIA score and
recovery of motor-evoked potentials and somatosensory evoked potentials
in a trial conducted on 20 adults with chronic SCI. Autologous stem cell
therapy administered intrathecally was shown to participate in
neuro-restoration via several pathways as suggested by the non-identical
effects recorded on different neurophysiological tests {[}\selectlanguage{english}12{]}.
Concerning safety, phases I/II clinical trials using autologous BM-MSCs
in patients with acute, subacute, and chronic SCI showed no long-term
side effects and seemed to be safe {[}\selectlanguage{english}13{]}.

SCI can be caused by various conditions, possibly resulting in permanent
impairment. On the other hand, MSCs and their associated cellular
products are readily available therapeutic tools for regenerative
medicine, including central nervous system diseases and conditions. The
ability of autologous BM-MSCs to release a range of antiapoptotic,
neurotrophic, and anti-inflammatory molecules is thought to be the cause
of their therapeutic effects {[}13{]}. These cells can differentiate
into neural cells, express neuronal markers, and secrete neuroprotective
growth factors that play a key role in neural restoration and
regeneration such as glia-derived, brain-derived, nerve, and ciliary
neurotrophic growth factors, and neurotropin-3 {[}13, \selectlanguage{english}14{]}. On the
other hand, cavitation prompted by tissue necrosis, axonal degeneration,
and neural cell death is frequently present with damaged neural tissue.
This invariably produces scars, which are made up of inflammatory immune
cells, fibroblasts, extracellular matrix (ECM) deposits, and astrocytes.
MSCs exhibit anti-inflammatory, anti-apoptotic, and ECM modulatory
properties, leading to neural rejuvenation {[}\selectlanguage{english}15{]}. All these
properties suggest that MSCs can be beneficial for spinal cord repair
and have provided an outline of strategies that scientists are taking
toward rejuvenation and restoration.

This case report shows promising improvement of SCI symptoms in our
patient. The Regentime therapy first show phenomenon was manifested
through the patient's early regain of sensation to touch progressively
during the first week following therapy. However, a longer follow-up
duration is yet to be undergone for further assessment of improvement
and any undesirable effects related to stem cell therapy.

\textbf{CONCLUSION}

SCI is a serious public health problem with a high morbidity rate. Stem
cell transplantation for SCI treatment has been conducted in several
studies showing promising results. Regentime therapy involves
administering autologous BM-MNCs to a target population. The
administration of this therapy to our SCI patient demonstrated the
`first show phenomenon' where he had improved symptoms as early as
during the first few days after therapy.

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