Biomedical Engineering Reference
In-Depth Information
formation. Angiogenetic growth factors (or genes encoding these proteins)
promote the development of collateral arterioles, the process known as “therapeu-
tic angiogenesis” or “neovascularization” [
6-
16
] .
The next part of this chapter has data related to practical aspects of SC harvest-
ing, ex vivo manipulation, as well as therapeutic application (transplant) for treat-
ment of patients with different hematological and other malignant or benign
disorders. In a nutshell, SC transplant involves the administration of high-dose
radio-chemotherapy and (re)infusion of collected cells to obtain abolition of dis-
ease, as well as to get hematopoietic reconstitution and general clinical improve-
ment of patient's status. SC transplant with reduced-intensity conditioning (RIC)
can be offered to patients who are ineligible for high-dose conditioning due to their
age or co-morbidities [
17-
19
]. Malignant hematological diseases have so far been
the most common indication of this new treatment modality; it has been less often
used for nonmalignant diseases. Nowadays BM and peripheral blood (PB) SC trans-
plants are more common in adult allogeneic or autologous setting. Umbilical cord
blood (UCB) transplants have provided hopeful results in pediatric settings, mainly
when a matched unrelated SC donor is impossible to obtain [
20-
24
] .
Therefore, in practice for therapeutic use SCs can be collected by (a) multiple
aspirations from BM; (b) cell harvesting by apheresis from peripheral blood after
mobilization with chemotherapy and/or growth factors (rHuG-CSF); and (c)
purification by processing from UCB. SCs collected from the stated sources can be
clinically applied (transplanted) immediately following harvesting (allogeneic set-
ting) or after a short-term storage in liquid state or a long-term storage in frozen
condition—cryopreservation (autologous setting) [
2,
5,
6,
25-
29
] .
The Type and Influence of the Stem Cell Source
Bone marrow-derived stem cells
. Historically, BM was the first source of SCs for
transplant in experimental and clinical setting [
30-
35
]. A marrow harvest is the
same for an allogeneic donor as for an autologous patient. SCs are collected by
multiple aspirations from the posterior and anterior iliac crest and (seldom) from
sternum. The posterior iliac crest provides the richest source of marrow. The proce-
dure is performed under sterile conditions in the operation room, while the donor is
generally anesthetized. In order to provide required number of nucleated cells
(TNCs), that is, ³ 3 × 10
8
/kg of body mass (kgbm), around 200 aspirations are
required, where single aspirate volume is 2-5 mL. Immediately after the collection,
cell aspirate should be filtered in order to remove bone and lipid tissue particles and/
or cell aggregates. Anticoagulation is provided using solution containing citrate and
by heparin diluted in saline (5,000 IU/500 mL), using autologous plasma or one of
the cell culture medium for resuspension of collected cells [
5,
6,
25,
26
] .
The target dose of collected marrow is 10-15 mL/kgbm. Thus, the volume of aspi-
rate is relatively large (800-1,000 mL) and contains a high count of red blood cells.
Accordingly, in order to prevent anemia in donors, blood for autologous transfusion
should be collected around one week before SC collection and transplant [
36
] .
