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Stem cells Loaded with Expectations

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resident in bone marrow and many other tissues ... 1700 embryology. 1997 cloning. 1998 inner cell mass culture. 2000 combinant techniques ... – PowerPoint PPT presentation

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Title: Stem cells Loaded with Expectations


1
Stem cells Loaded with Expectations
  • -
  • Petri Lehenkari
  • Department of Surgery
  • University of Oulu
  • Finland
  • -

2
All healing in adult tissue is facilitated by
stem cells
  • Totipotent stem cell
  • -embryonal cells before division into inner and
    outer cells
  • Pluripotent stem cell
  • -emryonal cells (inner cells)
  • Multipotent
  • -adult stem cells
  • -resident in bone marrow and many other tissues

3
Adult multipotent stem cells somatic stem
cells have been isolated from several tissues
Leonardo Da Vinci
  • Bone marrow, muscle, liver, spleen, tendon, fat,
    prepatellar fat body, brain, skin, gut

4
The classical idea of cell differentiation and
tissue regeneration is challenged by the modern
cell biology
Paul Berg,Stanford Univ
5
Examples of self-renewal in the adult body
  • Cut mucosa renewed at 2hrs -2 days
  • Skin renewal at 20 days
  • Heart remodeling at 5 years
  • All bones rebuilt at 10 years
  • Brain tissue remodelled at 20 years
  • Growing evidence suggests that all this renewal
    of human body is facilitated by adult stem cells

Le Corbusier
6
Cloning of differentiated cells has revealed the
multipotency of all cells
  • Any somatic cell can be dedifferentiated and
    returned into stem-cell-stage
  • Growth arrest and serum starvation (protein
    synthesis depletion) restores the multipontency
    of the nucleus
  • Wilmut I et al (Edinburgh, UK) Nature
  • 1997 Feb 27385(6619)810-3

7
Implications of the adult stem cell paradigma
  • Aging
  • -insufficient stem cell capacity? (dementia,
    osteoporosis, malabsorption, infections)
  • Disease
  • -inappropriate stem cell behavior (scarring in
    spinal chord injury, artery wall calcification
    and bone formation within, cancer)

8
Stem Cell Research has two traditions
  • Embryonal stem cells
  • 1700 embryology
  • 1997 cloning
  • 1998 inner cell mass culture
  • 2000 combinant techniques
  • 2003- therapeutic cloning, human-mouse chimera
  • Adult stem cells
  • 1959 bone marrow transplantation between
    identical siblings E. Donnall Thomas
  • 1968 Friedensteins exsperiments bone marrow
    cells differentiate into mesenchymal tissues
  • 1970-1980 Fliedner and Körbling bone marrow stem
    cells can be mobilised into peripheral
    circulation
  • 1999- Friedensteinin studies are rehabilitised at
    USA
  • 2001- donor cells are found in unexpected
    tissues experimental studies begin

9
Stem Cell Research in Finland
  • National Technology Agency Inquiry 2003
  • 35 research groups focused on stem cell research
    (140 persons)
  • Both embryonic and adult stem cell research
  • Resourcing by Public Bodies
  • TEKES, Finnish Academy, Government directly
  • Academic research accentuated at the moment

10
Stem Cell ethics in Finland
Misha Gordin
11
Stem Cell Group Oulu is interested in Adult Stem
Cells(somatic stem cells)
  • Because their use is ethically acceptable
  • Bone marrow transplantation is already at
    clinical use
  • Bone marow stem cells are a hot topic and new
    applicable data is produced rapidly
  • Bone marrow stem cells can easily be induced into
    bone cells
  • Clinical applications for bone repair are obvious

12
Oulu Stem Cell Team -aim
  • To culture somatic stem cells and develop
    clinical applications

13
Bone Marrow Stem Cell Cultures at OUH (Oulu
University Hospital)
  • Bone marrow derived mesenchymal stem cells have
    been cultured from 146 patients (age 2-98 years)
    between 2000-2004, urothelial stem cells cultured
    from 12 patients
  • Stem Cell Bank of 110 donors, SOP and GC
    protocol, ethical committee approval for
    research and 5 clinical autologous
    trasplantations for congenital pseudoarthrosis
    patients
  • First autologous osteoblast trasplntation back
    into patient done at 6.4.2004

14
Clinical trials
  • Phase 1
  • -proof of safety
  • Phase 2
  • -proof of effectivity
  • Phase 3
  • -proof of clinical usability

15
NF-1 (neurofibromatosis) Bacground for patient
selection
  • NF-1 Skeletal manifestations
  • -osteoporosis
  • -congenital tibial pseudoarthrosis

16
Transplantation of cells back into patients
principle of the phase 1 clinical trials
Bone marrow is harvested from iliac crest and
grown in culture
Tibial Nonunion
2 weeks of culture
Live implants
Cells in solution
Implantation of bone marrow cells into bone
defect with or without carrier
Osteoinduction occurs, healing the bone defect?
17
Cells in a carrier live implants
  • ALP staining, red color bone cells

With cells
Wo cells
Cells on plastic (bone cell differentiation Marked
with red color)
18
Cells embedded in the collagen carrier vs cells
in solution
  • 3 microbiological check ups (bacterial etc
    cultures, pcr) are performed prior to green for
    transplantation

19
Cell culture facilities are located adjescent to
the operation theatre
Operation theathres
Cell culture
20
Patients own bone marrow cells are multiplied in
culture
  • At beginning 100.000-200.000 mesenchymal stem
    cells from 15 ml of bone marrow
  • After 2 weeks 20-30.000.000 cells, both in
    solution and in collagen carriers

21
Cells embedded in the collagen carrier vs cells
in solution
  • Application in practise

22
Cells embedded in the collagen carrier vs cells
in solution
  • Application in practice

23
Results?
  • Aim to prove clinical safety
  • Not to prevent the amputation!
  • Postoperation
  • -no pain
  • -no acute adverse effects
  • -no acute infection problems
  • Control at 5-6 months after transplantation
  • -no signs of infection
  • -patient nro 2 benefits from transplantation
  • Patient nro 1 has healed first fracture but
    develops a new fracture

24
Clinical trials
  • Phase 1
  • -proof of safety
  • Phase 2
  • -proof of efficacy
  • Phase 3
  • -proof of clinical usability

25
Acknowledgements
  • Research teams in Oulu and in Turku
  • Dept of Pediatric surgery
  • Children and their parents!

26
The end!
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