Arteriosclerosis Obliterans by Autologous Transplantation of Bone Marrow Mononuclear Cells
Kazuteru Fujimoto', Hiroo Miyagi', Yuji Miyao', Ichiro Kajiwara', Youko Oe', Fumio Kawano^ and Michihiro Hidaka^
Division of 'Cardiovascular Medicine and ^Internal Medicine, National Hospital Organization Kumamoto Medical Centerl-5 Ninomaru, Kuma- moto, Kumamoto, Japan
Summary. A 60 year-old man with atherosclerosis obliterans had received a bypass operation twice, but came to notice resting pain in the left calf.
As it was not possible to perform further bypass operations (resulys of ar- teriography), we conducted conservative treatments. We therefore per- formed therapeutic angiogenesis by autologous transplantation of bone marrow mononuclear cells since the symptoms were not improved at all.
Resting pain was improved the next day after the operation and completely disappeared on the third day. The patient was only able to walk 180m in the preoperative state by crutch-assisted, but walked 180m without a stick on the second day and 900m on the fourth day. This treatment did not cause any inconvenience in everyday life and the patient showed no resting pain eight weeks later. In addition, the ankle-brachial index improved to 0.48 from the preoperation level of 0.36 after two months.
Therapeutic angiogenesis by autologous transplantation of bone marrow mononuclear cells was very usefijl.
Key words. Arteriosclerosis obliterans, Angiogenesis, Bone marrow
mononuclear cells
Introduction
Neovascular formation in adults has been considered to result exclusively from the formation of new blood vessels by sprouting of preexisting ma- ture endothelial cells, a process referred to as angiogenesis(Folkman J,
1995, Schper W, et al. 1971, Risau W, 1997). In contrast, vasculogenesis is referred to as the creation of primordial blood vessels from endothelial progenitor cells(Risau W, 1997, Risau W, 1995, Risau W, et al. 1988).
Recently, circulating endothelial progenitor cells have been discovered in adult peripheral blood and human umbilical cord blood(Asahara T, et al.
1997, Murohara T, et al. 2000). Circulating endothelial progenitor cells have been shown to accumulate at active angiogenic sites and to partici- pate in neovascularization(Takahashi T, et al. 1999). Endothelial progeni- tor cells in adults originate from bone marrow, and recently it has been demonstrated that implantation of autologous bone marrow mononuclear cells effectively augmented ischemia-induced neovascularization in animal studies (Shintani S, et al. 2001). as well as in human trials (Tateishi- Yuyama E, et al. 2002). Therapeutic angiogenesis is effective for limb salvage in patients with critical limb ischemia.
Case
A 60 year-old man with atherosclerosis obliterans had received a bypass operation twice, but came to notice resting pain in the left calf Using arte- riography, good collaterals were recognized in the left femoral region, but, less so in the knee region, therefore a bypass was impossible. Conservative treatments such as oral administration of aspirin and breaprost sodium with drip infiision of alprostadil were tried, but none of the symptoms were im- proved. So we induced therapeutic angiogenesis by autologous transplan- tation of bone marrow mononuclear cells.
Under general anesthesia, we gathered about 200ml of bone marrow from both iliac crests. Bone marrow mononuclear cells were isolated from the bone marrow by CS 3000 (Baxter company) and we obtained I.OXIO' cells. We injected the bone marrow mononuclear cells into the left calf and the sole.
Resting pain was improved after the operation next day and completely
disappeared on the third day (Fig. 1).
10
J) 6
2
preope. 1 St day 2nd day 3rd day 4th day
Fig. 1. shows the pain score. We showed a preoperative pain for ten. The pain score was five on the first day and zero on the second day.
The patient was only able to walk 180m by, but improved to 180m white walking without a stick on the second day and increased to 900m walking on the fourth day (Fig. 2).
1000 r 900 i 800 I 700 r 600 j 500 - 400 - 300 r 200 100 r
0 '-
1st day 2nd day 3rd day 4 t h day
Fig. 2. shows the distance that he could walk. Only 180m were able to walk by
preoperative crutch walking, but he came by 180m walk without a stick on the
second day and came to cut it by 900m walk on the fourth day.
He did not have any incoveriences in everyday life and showed no rest- ing pain eight weeks later. In addition, ankle-brachial index was improved to 0.43 one week later, 0.42 two weeks later, 0.42 three weeks later, 0.45 four weeks later and 0.48 eight weeks later from the preoperation 0.36 (Fig.3).
The symptoms were improved remarkably but, the arteriography sug- gested that collaterals did not clearly increase.
0.6
0.5
0.4
5 0.3
<
0.43 0.42 0.42
0.45 0.47
0.36
0.2
0.1
preope. 1week 2weeks 3weeks 4weeks Sweeks
