Bukti Klinis

Penggunaan Stem Sel &

Eksosom untuk Terapi COVID-19
Dr. dr. A Bambang Darwono, SpB., SpOT(K)., FICS
Penggunaan Stem Sel & Eksosom
● Dengan cara penyuntikan melalui pembuluh darah vena
● Stem Sel dan Eksosom masuk sirkulasi darah kecil menuju
jantung kanan dan dipompa menuju paru sampai di alveolus

Apakah stem sel tetap hidup di jaringan paru

atau hanya ‘short-lived’?
● Ternyata hanya short-lived, setelah 24 jam tidak ditemukan lagi,
live stem sel di jaringan paru
Apa yang masih bekerja di
jaringan paru yang bekerja
adalah:
● Paracrine ‘bystander’ effects
● Paracrine merupakan produk
stem sel
Komunikasi Antar Sel
Didalam Tubuh
1. ‘Contact-dependent’ antara sel
dengan sel, digunakan pada ‘cell
therapy’
2. ‘Cell-free therapy’ :
● Endocrine
● Paracrine
● Exosome
 01 Exosome, extracellular vesicles, are another member of
cellular secretome, acting as both a paracrine messenger affecting
adjacent cells and a systemic messenger circulating in the blood

Multivesicular body-derived vesicle,

02 Smallest size vesicle 30-120 nm

03
Exosome develop from the in-building of Endosome, which in turn

Exosome
forms Multi-Vesicular Bodies (MVBs) that contain Intraluminal
Vesicles (ILVs)

Exosome was originally disregarded as a simple vesicle

Now has become a Hot Research Topic that has
attracted attention of researches worldwide 04 The MVBs then fuse with the cell membrane of various cell types to
release ILVs extracellularly as Exosomes, which then serve as
messenger communicating with other cells

05 Function as important intercellular communication

mediator regulating the exchange of proteins and genetic materials
between donor and surrounding cells

Source: https://www.iba-lifesciences.com/exosome-isolation.html
 EKSOSOM
Vesikel yg berasal dari ‘Multivesicular body’
Ukuran sangat kecil 30-150 nm
Eksosom berfungsi sebagai mediator komunikasi antar
sel yang sangat penting, untuk mengatur pertukaran
protein dan material genetik antara donor dengan sel
disekitarnya.

Eksosom awalnya diabaikan dan dianggap tidak berguna,

Saat ini menjadi topik penelitian terkemuka
dan menarik perhatian para peneliti di
seluruh dunia
 EKSOSOM adalah
kendaraan berukuran
nano untuk mengangkut
muatan/kargo
Urine, saliva, air
susu, cairan otak
atau LCS

Mengantarkan
muatan kargo
ke sel Tubuh
Kunci Utama adalah:

Eksosom harus Eksosom sebagai MSCs yang sehat ada di

dalam embrio atau
berasal dari MSCs kendaraan nano diunduh dari tali pusat
yang sehat harus membawa bayi sehat dan
Kargo yang sehat dilahirkan dari Ibu yang
sehat
Role of Exosome in Regeneration
STEM CELLs Potency and Differentiation

Such horizontal transfer is implicated in recapitulating

Stem cells secrete extracellular vesicles (EVs) variety of stem cell features in recipient cells, such as:
carrying non-coding RNAs (ncRNAs) that are pluripotency, differentiation, maintenance and
transported to other cells ability to facilitate regenerative processes

EV-mediated transport of ncRNAs elicits regulatory Intercellular communication

programs in recipient cells: maintain tissue homeostasis without direct cell - cell contact
and immune regulation that may favor repair processes
01 Immune regulation (homeostasis
& neoplasia-disregulation)
Tissue repair,
regeneration 02
Important Key Point 03 Spread of infection disease
or cancer metastasis
Epigenetic changes
(miRNA) promoters 04
Exosome should Exosome as a nano
be derived from vehicle should carry
healthy MSCs healthy cargo
Preclinical Animal Model Study ( Bench )
Spinal Cord Injury

Before Treatment Outcome

SURGERY TO CREATE SCI ON RAT SECRETOME TREATMENT:
33 Sprague “ ARTIFICIAL COMPLETE SCI “ HEALED FASTER compared to CONTROL

Dawley white
male RATs.
7th days after treatment 14th days after treatment
Weight 200 -
300 gr. Age
2,5 - 3 months

GLIOSIS (G) , GLIOSIS RESPONS ,

DEMYELINATED DEGENERATED NEURON,
SCHWANN CELL (M) , CYSTIC FORMATION :
DEGENERATED NEURON “DECREASED”
B: Surgery; T: Treatment; S: Sampling (D) HE stain
HE stained
Case Report
Spinal Cord Injury & Stroke

Before Treatment Outcome

Male 48
(Sport Injury)

Vetebra T7 Burst Fracture

Complete SCI (Paraplegia ASIA “A“)
25th Month Treatment
Able to walk with KAFO and remove the Hip component

Male 69 14th Days after

(Tetra–parese) Secretome Injection
Hand’s function
improving
Start Swimming

Bed ridden, Neck & Back pain, and Convulsion 6th months later

Male 40 1,5 years ago stroke non hemorrhagic 4th Month Treatment
Operated craniotomy • Better communication
(Brain Injury) • Wheelchair, right hemiplegic • Able to walk without wheelchair
• Motoric aphasia & difficult in • No convulsion & tremor
communication
3 Pathways
of Exosome
 Case Report (Clinical Evidence – Bed Side)
COVID-19 Patient

Before Treatment Outcome

Female BP 110/70 mmHg BP 110/70 mmHg
(37)
Chief Complaints Chief Complaints
History of similar HR 66x/minute HR 66x/minute
• Fever (37.5) • No complaints
complaint (-) & Fatigue (+)
sistemic disease (-) RR 12x/minute • RR 12x/minute
• Back pain, soreness
• Lost the senses of taste After 4 days
T 37.5° C T 36.6° C
and smell treatment

BW 69 kg BW 69 kg

Ureum 38 ↓
Male BP 130/80 mmHg
(73) Creatinine 2,6↓ Chief Complaints
99x/minute Chief Complaints
History of similar HR
• Fever (+) • No fever
complaint (-) & Uric Acid 4,9 No fatigue
sistemic disease (-) RR 22x/minute • Fatigue (+) •
• Vomiting (+) • No vomiting
• Severe headache (+) • No headache
T 41.9° C
• Respiratory symptoms (+) • No respiratory symptoms

47 kg After 21 days
BW
treatment
 Case Report (Clinical Evidence – Bed Side)
COVID-19 Patient

Before Treatment Outcome

Female BP
140/90 mmHg BP
140/90 mmHg
(35) Chief Complaints Chief Complaints
History of similar
HR
88x/minute HR 88x/minute
• Fever (39.7) • No complaints
complaint (-) & RR 22x/minute RR 12x/minute
sistemic disease (-) • Fatigue (+)
T 39.7° C • Back pain, soreness T 36.6° C After 5 days
• Lost the senses of taste treatment
BW 45 kg and smell BW 45 kg
Swab (+) Swab (-)
Male
BP
140/90 mmHg 140/90 Chief Complaints
(39) BP

Chief Complaints mmHg • No fever

History of similar HR 90x/minute HR
• Fever (+) 80x/minute • No fatigue
complaint (-) & RR 22x/minute
sistemic disease (-) • Fatigue (+) RR • No vomiting
20x/minute
Nausea (+) • No headache
T 39° C •
T 36 C
• headache (+) • No respiratory symptoms
BW 70 kg 70bkg
• Respiratory symptoms (+) BW
Swab (+) Swab (-) After 17 days
• Cough (+) Treatment
 Case Report (Clinical Evidence – Bed Side)
COVID-19 Patient

Before Treatment Outcome

Female BP
135/85 mmHg BP 120/80 mmHg
Chief Complaints
(54) HR
96 x/ minute HR 85 x/ minute
• High fever (+) • No fever
History of similar
RR 22 x/ minute RR 20 x/ minute • No fatigue
complaint (-) & • Fatigue (+)
Sistemic disease (-) • No vomiting
T 42° C • Vomiting (+) T 36,6° C • No headache
• Severe headache (+) • No respiratory symptoms
BW 52 kg BW 52 kg
Swab (+) Swab (-)
After 9 days
Chest CT: normal

After 8 months
REINFECTION

RECOVER after 7 days

 Case Report ( Clinical Evidence – Bed Side )
COVID-19 Patient

Before Treatment Outcome

BP 130/90 mmHg BP
130/90 mmHg
Female (60)
HR 80x/minute Chief Complaints HR 80x/minute Chief Complaints
History of similar
• Fever (38) • No complaints
complaint (-) & RR 20x/minute RR 12x/minute
sistemic disease (-) • Fatigue (+)
T 38° C • Back pain, soreness T 36.1° C After 12 days
• Lost the senses of taste treatment
BW 56 kg and smell BW 56 kg
Swab (+) Swab (-)

BP 150/90 mmHg Chief Complaints

Male (65)
BP 150/90
HR 90x/minute Chief Complaints mmHg • No fever
History of similar HR
• Fever (+) • No fatigue
complaint (-) & RR
24x/minute 80x/minute
sistemic disease (-) • Fatigue (+) RR • No vomiting
20x/minute
T 39° C • Nausea (+) • No headache
T 36 C No respiratory symptoms
• headache (+) •
BW 72 kg 72 kg
• Respiratory symptoms (+) BW
Swab (+) Swab (-)
• Cough (+) After 23 days Treatment
Swab (-)
 Case Report (Clinical Evidence – Bed Side)
COVID-19 Patient

Before Treatment Outcome

BP 150/90 mmHg BP 140/90 mmHg
Female (33)
HR 80x/minute Chief Complaints HR 80x/minute Chief Complaints
History of similar
• Fever (39) • No complaints
complaint (-) & RR 20x/minute RR 12x/minute
sistemic disease (-) • Fatigue (+)
T 39° C • Head ache, soreness T 36° C After 24 days
• Lost the senses of taste treatment
BW 57 kg and smell BW 57 kg
Swab (+) Swab (-)

BP NA mmHg
Male (2) BP
NA mmHg
HR NA/minute Chief Complaints NA/minute
Chief Complaints
History of similar HR
• Fever (+) • No fever
complaint (-) & RR
NA/minute NA/minute
sistemic disease (-) • Fatigue (+) RR • No fatigue
39° C 36 C No vomiting
T • Vomiting (+) •
• headache (+)
T
15 kg • No headache
BW 15 kg Swab (-)
• Cough (+) BW
Swab (+) After 5 days
Symptomatic Treatment
 Thanks
bdarwono@hotmail.com
+628111180216