INDAH YULIANTO.,RATNA JUWITA,TITI MOERTOLO,SUBANDRIO, DEWI A,YUYUN HP, KALISTA.

APLIKASI KLINIS SEL PUNCA

Differentiation Human Stem Cells

Trans-differentiation

Why Stem Cells ?

By definition, a stem cell is characterized by its ability to self-renew and its ability to trans differentiate along multiple lineage pathways.

Self-renewal of stem cells

Asymmetric cell division

Symmetric cell division

Morrison & Kimble 2006

Self-renewal of stem cells

Asymmetric cell division : to maintain the stem cell number

A. Intrinsic asymmetric cell division

B. Extrinsic (Eviromental) asymetric cell devision

Morrison & Kimble 2006

Intrinsic asymmetric cell division

One stem cell divides into two daughter cells,

which are different from each other.

One of daughter cells is similar to the parental cell and

The other daughter cell becomes progenitor cell, which will eventually differentiate into tissue committed resident cell.

Distinguish features of progenitor/precursor cells and Stem cells

Symmetric cell division

Daughter cells

Stem cells NICHE

The microenvironment in which stem cells are found.

The microenvironment interacts with stem cells to regulate stem cell fate.

Various niche factors act on stem cells to alter their gene expression, and induce their proliferation or differentiation.

Stem Cells NICHE

Niche factors include: 1. cell-cell interactions between stem

cells, 2. interactions between stem cells and

neighboring differentiated cells, 3. interactions between stem cells and

extra-cellular matrix components, adhesion molecules,growth factors, cytokines and physiochemical nature of the microenvironment.

4. Niche has both anatomic and functional dimensions.

Can be found in abundant quantities (millions to billions of cells)

Can be harvested by a minimally invasive procedure

Can be differentiated along multiple cell lineage pathways in a regulatable and reproducible manner.

Can be safely and effectively transplanted to either an autologous or allogeneic host

Regenerative medicinal applications should meet the following criteria:

Overview of Healing response after injury

Goal of The Wound HealingReconstruction of :

Original Architecture Function of the injured tissue.

(Cotran et.al. 1999., Majno & Joris 2004)

Cotran et al. 1999, Majno & Joris 2004

Cotran et al. 1999, Majno & Joris 2004

Cotran et al. 1999, Majno & Joris 2004

Tissue Wound Healing

Repair Regeneration

(Majno & Joris 2004, Kumar et al. 2009)

Tissue Repair

Replacement of injured tissue by different tissue, usually by fibrosis or scar

(Kumar et al. 2009, Majno & Joris 2004)

Tissue Regeneration

Replacement of injured tissue by the same resident cells, or by differentiation of progenitor/stem cells into tissue committed cells.

(Kumar et al. 2009, Majno & Joris 2004)

PERANAN BERBAGAI KOMPONEN PADA “NICHE” JARINGAN KULIT(Copyright © 2012 VictorW.Wong et al.)

Stem Cells Transplantation

Autologous Allogeneic : from individuals belonging to

the same species but genetically dissimilar (and hence immunologiccally incmpatible)

Syngeneic : between geneticcally identical individual (tween)

Xenogeneic : From individuals of different species (hence of disparate cell type)

Adult (Somatic) Stem Cells

Hematopoietic stem cells (HSC)

Mesenchymal stem cells (MSC)

Endothelial progenitor cells (EPC)

Neural stem cells

Hepatic stem cells

etc.

Adipocyte Stem Cells

Why Adipocyte Tissue ?

Bone marrow harvest (2)

Flow Chart Elucidating possible commitment, lineage progression and maturation ADMSCs

from Aldeman D., Alexander ,R.W.,PPM : Oct 2011

Hasil lemak dari liposuction

pellet

Adipocyte after 24 hours

Adipocyte after 24 hours

ADSC pasage 1 : hari ke 3

A. ADSCs hari ke 7 dan B. ADSC hari ke 14

A B

by dr Indah Yulianto – dr. Yuyun Rindiastuti

Alopecia Universalis : 1 month after MChSc and Product (AAPE)

Alopecia Universalis :1 month after MCSc + Product MSCc

By Indah Yulianto

After 2 Months

After :2 Months

By Indah Yulianto

After 4 months

http://content.nejm.org/content/vol351/issue22/images/large/02f1.jpeg

EPC : Primer Culture

Courtesy by : Yuyun, Wiwied & Yenni

80% 100%

SECRETOME FROM HUVEC (HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS) from patient Alopecia

Areata for more than 10 years.

Secretome from HUVEC

Homing and Trafficking Mesenchymal Stromal cells to sites tissue injury after infusion

Neuroischemic lesion of fifth metatarsal with application : EPC & amnion membrane (2 months)

Courtesy : By Indah Yulianto, &Yuyun Rindiastuti

Female patient (64 years old) with Basaloma in her left cheek

Preparing Secretome from Wharton Jelly

BASALIOMA(Surgery + Secretome fetal

Endothelial progenitor Cells / EPC)

Peeling the amniotic membrane from the placenta

(Once again using Hypoxia methode)

Figure 1: Processing of amniotic membrane.

Amniotic membrane in its preserving fluid

Preparation of the amniotic membrane and the wound dressing interface before

placement of a wound dressing.

No healing ulcer (1 month) post op- Squamous Cell Carcinoma Surgery in Head

(Male, 84 yr)

Placing AMNION

Wound Regeneration after 2 Surgeried : SCC and

UNSECCESSFUL Dermagraft

Healing Process with renewaldamage tissue

AMNIOTIC MEMBRANE DRESSINGPROMOTES EPITHELISATION & GRAANULATION

+ INJ EPC

1.5 MONTH AFTER

CLI – post AmputationEPC + Amnion membrane

What kind of Stem cells that we Need ?

Acne Papulo pustular + Scar Acne : before and 1 week after AAPE

(3) Scar acne pasca skin needling + product & (4) 1 week after skin needling + MCSs +_ Product

34

Acne Papulo Pustular + Scar

Courtesy by dr Titik Moertolo

1 month after Skin Needling + MShCs

Acne Scar & Box scar 1 week post Dermaroller

Acne Scar before (Box Scar)2 weeks after Skin Needling +

MShCs

Courtesy by dr Titik Moertolo

Infant 2 weeks, with fistula supra ani

Tissue regeneration after 1 week using MshCs Product - Cream

BY Indah Yulianto

Fistula – Before

Therapy

One week after

1 Year after – no Scar

Leprosy after 30 years + 3 months burning

ulcer + Infection

3 weeks after MSCs Product Injections +

Cream

BY Indah Yulianto

Apr 12, 2023 68

Male 23 yr, Combutio more than 5 months : Injections and Topical :HUVECs (Spheroid and Hypoxia)

Luka bakar + infeksi 5 bulan y.l.

intra kutan produk MShCs

Pengolesan Krem + Produk MShCsHari ke 15 : penyembuhan 75% tanpa Cicatriks ataupun Retraksi persendian

regenerasi

Apr 12, 2023 70

Starting to heal and without scar

after 2 months

ACNE CONGLOBATA and Scar : USING‘HUVEC’

AUTISM AND PARAPLEGIA (FEMALE CHILD – 4 YEARS : USING HUVEC : 2 TIMES)

Multiple sclerosis , Asthma Bronchiale, Parkinson and Ventricle heart disease

Apr 12, 2023 74

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